PROTECTED DEOXYDIDEHYDRO-NUCLEOSIDES TECHNICAL FIELD The invention relates generally to protected intermediates in the synthesis of nucleotide analogue drugs. In particular, the invention relates to the synthesis of protected nucleoside compounds which can be used as intermediates in the synthesis of 3′-deoxy- 3′,4′-didehydro-nucleosides and related compounds. BACKGROUND OF THE INVENTION The recent emergence of the COVID-19 pandemic has brought widespread attention to the impacts viruses can have on human life and healthcare systems. Viruses are implicated in the majority of epidemic and pandemic diseases, which reflects their high transmissibility and the paucity of effective antiviral therapies. In the absence of vaccines, treatment of emergent and re-emergent viruses relies on the repurposing of existing drugs and therefore the development of broad-spectrum antiviral drugs is of great value. Attainment of this goal is challenging as viruses are obligate parasites which employ host cell machinery and present fewer druggable targets compared to other pathogens. Nevertheless, a number of nucleotide analogues which target viral proteins such as RNA- dependent RNA polymerases (RdRp) and DNA polymerases do exhibit broad-spectrum activity and constitute an important class of antiviral drugs. See, for example, the following drugs: Viperin (Virus Inhibitory Protein, Endoplasmic Reticulum-associated, Interferon- inducible), also known as RSAD2 (radical SAM domain-containing 2), is one of eight known radical SAM enzymes encoded in the human genome, and its expression is induced by interferon pathways in response to viral infection. Viperin inhibits replication of both RNA and DNA viruses by diverse mechanisms, including protein-protein interactions and modulation of immune-signalling, thereby contributing to the innate antiviral response. The role of 3′-deoxy-3′,4′-didehydro-cytidine triphosphate (ddhCTP) in the antiviral activity of viperin is still not completely understood. However, it is thought to compete with cytidine triphosphate (CTP) for Flaviviridae RdRps (dengue virus, West Nile virus, Zika virus and hepatitis C virus) resulting in obligate chain termination and inhibition of viral genome replication. Modelling and biochemical studies also suggest that ddhCTP can inhibit NAD ⁺ - dependent enzymes, leading to downstream and/or upstream effects in metabolic/signalling pathways. Importantly, ddhCTP production does not affect the viability or growth rate of Vero and HEK293T cells. ddhCTP and 3′-deoxy-3′,4′-didehydro-cytidine (ddhC) therefore represent a promising platform for the development of broad-spectrum antiviral agents. However, the synthesis of ddhCTP, and related compounds, can be challenging and improved synthetic routes are needed for the more efficient and cost-effective development of this important class of compounds. The applicant has now developed a protecting group strategy to provide a convenient synthesis of important intermediate compounds useful for the synthesis of, not only ddhC and related compounds, but a broad range of 3’-deoxy-3’,4’-didehydroribonucleosides including compounds derived from both natural and non-natural nucleosides. The invention seeks to address the need for improved methods of synthesising 3’- deoxy-3’,4’-didehydroribonucleoside based antiviral drugs by providing a novel class of compounds useful as intermediates in the synthetic process. SUMMARY OF THE INVENTION In one aspect the invention provides a compound of the Formula (I) or Formula (Ia): wherein: X1 is a silyl ether protecting group; Y is H, C _1-3 alkyl, C _2-3 alkenyl, or C _2-3 alkynyl; A is selected from: wherein: R ₁ and R ₂ are each H, OH, OX ₂ where X ₂ is a silyl protecting group, or a C _1-6 alkyl, C _1-12 acyl, C _1-6 alkoxymethyl, C ₃ -C ₁₂ cycloalkyl, alkyloxycarbonyl, aryl, aryloxy or aryloxymethyl group each of which is optionally substituted with one or more alkyl, alkenyl, alkynyl, alkoxy, aryl, aryloxy, amino, halo or hydroxy groups; or R ₁ and R ₂ taken together form a cyclic group optionally substituted with one or more alkyl, alkenyl, alkynyl, alkoxy, aryloxy, amino, halo or hydroxy groups; R ₃ and R ₄ are each H, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, haloalkyl, or halogen; R ₅ is H, C _1-12 alkyl, C _1-12 acyl, C _1-6 alkoxymethyl, acyloxymethyl, or aryloxymethyl; R ₆ is H, or a C _1-6 alkyl, aryl, C _1-12 acyl, alkoxycarbonyl, arylthioethyl, arylsulfonylethyl, cyanoethyl, alkylsilylethyl, or arylethyl group each of which is optionally substituted with one or more alkyl, alkenyl, alkynyl, alkoxy, aryloxy, amino, halo, nitro, cyano or hydroxy groups; and * denotes a point of attachment to the Formula (I) ring or Formula (Ia) ring. In certain embodiments of the invention the compound is a compound of Formula (I). In other embodiments the compound is a compound of Formula (Ia). In certain embodiments of the invention X1 is an alkylsilyl group or an arylsilyl group. For example, in some embodiments the alkylsilyl group is trimethylsilyl (TMS), triethylsilyl (TES), t-butyldimethylsilyl (TBDMS), or triisopropylsilyl (TIPS). In other embodiments the arylsilyl group may be t-butyldiphenylsilyl (TBDPS). In certain embodiments of the invention Y is H. For example, in some embodiments Y is C _1-3 alkyl, such as methyl. In certain embodiments of the invention A is: In some specific embodiments A is: In other embodiments of the invention A is:

In some embodiments of the invention R ₁ or R ₂ is benzoyl (Bz) optionally substituted with a methoxy group or a halo group, 9-fluorenylmethoxycarbonyl (Fmoc), t-butoxy carbonyl (Boc), benzyloxy carbonyl (Cbz), acetyl (Ac), trifluoroacetyl, benzyl (Bn) optionally substituted with a methoxy group or a halo group, triphenylmethyl (Tr), methoxytriphenylmethyl (MTr), dimethoxytriphenylmethyl (DMTr), p-toluenesulfonyl (Ts), isobutyryl, propionyl, or pivaloyl. In other embodiments R ₁ or R ₂ taken together is phthalimide or benzylideneamine. In yet other embodiments one of R ₁ and R ₂ is H and the other is OH or OX ₂ . In some embodiments of the invention X ₂ is an alkylsilyl group or an arylsilyl group. For example, in some embodiments the alkylsilyl group is trimethylsilyl (TMS), triethylsilyl (TES), t-butyldimethylsilyl (TBDMS), or triisopropylsilyl (TIPS). In other embodiments the arylsilyl group is t-butyldiphenylsilyl (TBDPS). In certain embodiments of the invention R ₃ and R ₄ are each H, methyl or trifluoromethyl. In certain embodiments of the invention R ₅ is H or methyl. In certain embodiments of the invention R ₆ is H, methyl, benzyloxy, 2- (phenyl)thioethyl, 2-(4-nitrophenyl)thioethyl, 2-(phenyl)sulfonylethyl, 2-(4- nitrophenyl)sulfonylethyl, 2-cyanoethyl, 2-(trimethylsilyl)ethyl, 2-(4-nitrophenyl)ethyl, or 2- (4-cyanophenyl)ethyl. In certain embodiments of the invention R ₁ is H and R ₂ is benzoyl. In certain embodiments of the invention the compound has the Formula (II) or the Formula (IIa): . In a second aspect the invention provides a process for the preparation of a compound of Formula (I) or Formula (Ia) comprising the steps: i. reacting a nucleoside of the Formula (III) or Formula (IIIa) with a silyl protecting reagent to protect the hydroxyl groups at the 2’ and 5’ positions with silyl protecting groups wherein: Y is H, C _1-3 alkyl, C _2-3 alkenyl, or C _2-3 alkynyl; A is selected from:

wherein: R ₁ and R ₂ are each H, OH, OX ₂ where X ₂ is a silyl protecting group, or a C _1-6 alkyl, C _1-12 acyl, C _1-6 alkoxymethyl, C ₃ -C ₁₂ cycloalkyl, alkyloxycarbonyl, aryl, aryloxy or aryloxymethyl group each of which is optionally substituted with one or more alkyl, alkenyl, alkynyl, alkoxy, aryl, aryloxy, amino, halo or hydroxy groups, provided R ₁ and R ₂ are not both H; or R ₁ and R ₂ taken together form a cyclic group optionally substituted with one or more alkyl, alkenyl, alkynyl, alkoxy, aryloxy, amino, halo or hydroxy groups; R ₃ and R ₄ are each H, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, haloalkyl, or halogen; R ₅ is H, C _1-12 alkyl, C _1-12 acyl, C _1-6 alkoxymethyl, acyloxymethyl, or aryloxymethyl; R ₆ is H, or a C _1-6 alkyl, aryl, C _1-12 acyl, alkoxycarbonyl, arylthioethyl, arylsulfonylethyl, cyanoethyl, alkylsilylethyl, or arylethyl group each of which is optionally substituted with one or more alkyl, alkenyl, alkynyl, alkoxy, aryloxy, amino, halo, nitro, cyano or hydroxy groups; and * denotes a point of attachment to the Formula (III) ring or Formula (IIIa) ring; ii. substituting the hydroxyl group at the 3’ position with iodine; iii. removing the silyl protecting group from the 5’ position; and iv. removing the iodine from the 3’ position and hydrogen from the 4’ position to give the compound of Formula (I) or the compound of Formula (Ia). In some embodiments of the invention R ₁ or R ₂ is benzoyl (Bz) optionally substituted with a methoxy group or a halo group, 9-fluorenylmethoxycarbonyl (Fmoc), t-butoxy carbonyl (Boc), benzyloxy carbonyl (Cbz), acetyl (Ac), trifluoroacetyl, benzyl (Bn) optionally substituted with a methoxy group or a halo group, triphenylmethyl (Tr), methoxytriphenylmethyl (MTr), dimethoxytriphenylmethyl (DMTr), p-toluenesulfonyl (Ts), isobutyryl, propionyl, or pivaloyl. In other embodiments R ₁ or R ₂ taken together is phthalimide or benzylideneamine. In yet other embodiments one of R ₁ and R ₂ is H and the other is OH or OX ₂ . In some embodiments of the invention X ₂ is an alkylsilyl group or an arylsilyl group. For example, in some embodiments the alkylsilyl group is trimethylsilyl (TMS), triethylsilyl (TES), t-butyldimethylsilyl (TBDMS), or triisopropylsilyl (TIPS). In other embodiments the arylsilyl group is t-butyldiphenylsilyl (TBDPS). In certain embodiments of the invention R ₃ and R ₄ are each H, methyl or trifluoromethyl. In certain embodiments of the invention R ₅ is H or methyl. In certain embodiments of the invention R ₆ is H, methyl, benzyloxy, 2- (phenyl)thioethyl, 2-(4-nitrophenyl)thioethyl, 2-(phenyl)sulfonylethyl, 2-(4- nitrophenyl)sulfonylethyl, 2-cyanoethyl, 2-(trimethylsilyl)ethyl, 2-(4-nitrophenyl)ethyl, or 2- (4-cyanophenyl)ethyl. In certain embodiments of the invention R ₁ is H and R ₂ is benzoyl. In certain embodiments of the invention A is: In certain embodiments of the invention the nucleoside of the Formula (III) or Formula (IIIa) is a 4-N-protected cytidine, for example 4-N-benzoylcytidine. In certain embodiments of the invention each silyl protecting group is an alkylsilyl group or an arylsilyl group. In certain embodiments the alkylsilyl group is trimethylsilyl (TMS), triethylsilyl (TES), t-butyldimethylsilyl (TBDMS), or triisopropylsilyl (TIPS). In certain embodiments the arylsilyl group is t-butyldiphenylsilyl (TBDPS). In certain embodiments of the invention the process is for the preparation of a compound of Formula (II) or Formula (IIa) comprising the steps: i. reacting a 4-N-benzoylcytidine with t-butyldimethylsilyl chloride to give 4-N- benzoyl-2′,5′-bis-O-(t-butyldimethylsilyl)cytidine; ii. reacting 4-N-benzoyl-2,5-bis-O-(t-butyldimethylsilyl)cytidine with methyltriphenoxyphosphonium iodide to give 1-(2’,5’-bis-O-(t- butyldimethylsilyl)-3’-iodo-β-threo-pentofuranosyl)-4-N-b enzoylcytosine; iii. removing the silyl protecting group from the 5’ position of 1-(2’,5’-bis-O-(t- butyldimethylsilyl)-3’-iodo-β-threo-pentofuranosyl)-4-N-b enzoylcytosine to give 1-(2′-O-(t-butyldimethylsilyl)-3′-iodo-β-threo-pentofur anosyl)-4-N- benzoylcytosine; and iv. treating 1-(2′-O-(t-butyldimethylsilyl)-3′-iodo-β-threo-pentofur anosyl)-4-N- benzoylcytosine with 1,4-diazabicyclo[2.2.2]octane (DABCO) to remove the iodine from the 3’ position and hydrogen from the 4’ position to give the compound of Formula (II) or Formula (IIa). In certain embodiments of the invention the process is for the preparation of a compound of Formula (II) where 4-N-benzoylcytidine in step i. is 4-N-benzoyl-D-cytidine. In other embodiments the process is for the preparation of a compound of Formula (IIa) where 4-N-benzoylcytidine in step i. is 4-N-benzoyl-L-cytidine. In another aspect the invention provides the use of a compound of the invention in the preparation of a 3’-deoxy-3’,4’-didehydro nucleoside monophosphate, diphosphate, or triphosphate of the Formula (IV) or the Formula (IVa): wherein A, X ₁ and Y are as defined above and Z is , or a salt thereof. DETAILED DESCRIPTION Definitions Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which the inventions belong. Although any assays, methods, devices and materials similar or equivalent to those described herein can be used in the practice or testing of the invention, various assays, methods, devices and materials are now described. It is intended that reference to a range of numbers disclosed herein (for example 1 to 10) also incorporates reference to all related numbers within that range (for example, 1, 1.1, 2, 3, 3.9, 4, 5, 6, 6.5, 7, 8, 9 and 10) and also any range of rational numbers within that range (for example 2 to 8, 1.5 to 5.5 and 3.1 to 4.7) and, therefore, all sub-ranges of all ranges expressly disclosed herein are expressly disclosed. These are only examples of what is specifically intended and all possible combinations of numerical values between the lowest value and the highest value enumerated are to be considered to be expressly stated in this application in a similar manner. As used in this specification, the words “comprises”, “comprising”, and similar words, are not to be interpreted in an exclusive or exhaustive sense. In other words, they are intended to mean “including, but not limited to”. The term “alkyl” means any saturated hydrocarbon radical and is intended to include both straight- and branched-chain alkyl groups. The term “C ₁ -C ₆ alkyl” means any saturated hydrocarbon radical having up to 6 carbon atoms. Examples include, but are not limited to methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-ethylpropyl, n-hexyl and 1-methyl-2-ethylpropyl. The term “alkenyl” means any hydrocarbon radical having at least one double bond and is intended to include both straight- and branched-chain alkenyl groups. Examples of alkenyl groups include, but are not limited to, ethenyl, n-propenyl, iso-propenyl, n-butenyl, iso-butenyl, sec-butenyl, n-pentenyl, 1,1-dimethylpropenyl, 1,2-dimethylpropenyl, , 1- ethylpropenyl, 2-ethylpropenyl, n-hexenyl and 1-methyl-2-ethylpropenyl. The term “alkynyl” means any hydrocarbon radical having at least one carbon- carbon triple bond and is intended to include both straight- and branched-chain alkynyl groups. Examples of alkynyl groups include, but are not limited to, ethynyl, n-propynyl and n-butynyl. The term “aryl” means an aromatic radical having 1 to 18 carbon atoms and includes heteroaromatic radicals. Examples include monocyclic groups, as well as fused groups such as bicyclic groups and tricyclic groups. Examples include, but are not limited to, phenyl, indenyl, 1-naphthyl, 2-naphthyl, azulenyl, heptalenyl, biphenyl, indacenyl, acenaphthyl, fluorenyl, phenalenyl, phenanthrenyl, anthracenyl, cyclopentacyclooctenyl, and benzocyclooctenyl, pyridyl, pyrrolyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazolyl, tetrazolyl, and imidazolyl. The term “alkoxy” means an OR group, where R is alkyl, alkenyl or alkynyl as defined above. The term “acyl” means a –(C=O)R group, where R is alkyl, alkenyl, alkynyl or aryl as defined above. The term “acyloxy” means an –O(C=O)R group, where R is alkyl, alkenyl, alkynyl or aryl as defined above. The term “alkoxycarbonyl” means an RO(C=O)- group, where R is alkyl, alkenyl or alkynyl as defined above. The term “aryloxy” means an OR group, where R is aryl as defined above. The term “aryloxycarbonyl” means an RO(C=O)- group, where R is aryl as defined above. The term “alkylene” means a diradical corresponding to an alkyl group and is intended to include straight chain alkyl groups. Examples of alkylene groups include, but are not limited to, methylene and ethylene. The term “protecting group” means a group that selectively protects an organic functional group, temporarily masking the chemistry of that functional group and allowing other sites in the molecule to be manipulated without affecting the functional group. Suitable protecting groups are known to those skilled in the art and are described, for example, in Protective Groups in Organic Synthesis (3 ^rd Ed.), T. W. Greene and P. G. M. Wuts, John Wiley & Sons Inc (1999). Examples of protecting groups include, but are not limited to, O-benzyl, O-benzhydryl, O-trityl, O-t-butyldimethylsilyl, O-t-butyldiphenylsilyl, O-4-methylbenzyl, O-acetyl, O-chloroacetyl, O-methoxyacetyl, O-benzoyl, O-4- bromobenzoyl, O-4-methylbenzoyl, O-fluorenylmethoxycarbonyl and O-levulinoyl. The term “silyl ether protecting group” is a protecting group such as O-t- butyldimethylsilyl and O-t-butyldiphenylsilyl. The term “nucleoside” means a compound that consists of a purine or pyrimidine base combined with deoxyribose or ribose and is found especially in DNA or RNA, and includes adenosine, cytidine, uridine and guanosine. Advantages of the invention The following are advantages of at least some embodiments of the invention. One advantage of 2’-silyl protection of the ddh-compounds is that this method allows selective chemical manipulation of the 5’-position to access compounds of interest containing a 3’-deoxy-3’,4’-didehydroribo-motif that are otherwise difficult to achieve. Installation of other protecting groups, such as alkyloxycarbonyl or acyl protecting groups, selectively in the 2’-position are fraught with difficulties, either by competing chemical pathways and decomposition of the 3’-deoxy-3’,4’-didehydroribo compound, or in their selective removal to obtain the desired 3’,4’-didehydroribo compounds. One advantage of the process of the invention is that it may be applied generally to a range of compounds, by commencing from the appropriate nucleoside analogue, which may be available from a commercial supplier, and choosing appropriate protection for the nucleobase substituent. The process affords direct access to 2’-silyl protected 3’-deoxy- 3’,4’-didehydroribo compounds by a very efficient synthetic route. This route is advantageous because it requires a low number of high-yielding chemical steps to obtain the 2’-silyl protected 3’-deoxy-3’,4’-didehydroribo compounds. The 2’-silylated intermediates in this process generally have good solubility in organic solvents which allows for simple practical handling. Other methods used to obtain 3’-deoxy-3’,4’-didehydroribo compounds rely on a 3’-deoxy-3’,4’-α,β-unsaturated 5’- carbonyl (aldehyde or ester) intermediate, which are very difficult to selectively derivatise owing to facile decomposition pathways. The process of the invention does not proceed via a 3’-deoxy-3’,4’-α,β-unsaturated 5’-carbonyl compound. Additionally, selective derivatisation of unprotected 3’-deoxy-3’,4’-α,β-unsaturated 5’-carbonyl compounds (3’- deoxy-3’,4’-didehydro 5’-carbonyl compounds) suffers from their general and usually prohibitive insolubility in organic solvents. Synthesis of compounds Synthesis of all ddhC compounds commenced from 4-N-benzoylcytidine (1), which was sourced from Biosynth Carbosynth ^® (Scheme 1).

The synthesis of compounds 6 and 7 closely followed procedures reported previously by Petrova et al. (Tetrahedron Letters, 2010, 51, 6874–6876). This approach involves Moffat-Pfitzner oxidation of the 5′-alcohol 6 to an aldehyde, which facilitates base-catalysed elimination of a 3′-orthoformate to generate the α,β-unsaturated aldehyde 7. Aldehyde 7, isolated after initial chromatography, was triturated from boiling hot ethyl acetate to afford pure product after cooling and filtration, and was found to be stable and storable at room temperature in this form. Aldehyde 7 was converted to TBDMS-protected intermediate 8. Aldehyde 8 was reduced with sodium borohydride in methanol to afford TBDMS-protected intermediate 5A. While the Moffatt-Pfitzner oxidation yielding aldehyde 7 afforded a viable synthetic route to 2′-O-TBDMS-protected intermediate 5A in satisfactory yields, the oxidation conditions were poorly reproducible. Efforts to find an improved oxidation procedure were unsuccessful. An alternative synthesis of the 3′-deoxy-3′,4′-dehydroribose ring system was subsequently developed around a strategy involving the elimination of a 3′-iodide in the xylo-configuration. Regioselective silyl protection (Can. J. Chem. 1978, 56, 2768–2780) of 4-N-benzoylcytidine (1), then iodination with triphenoxy methylphosphonium iodide (J. Org. Chem. 1970, 35 (9), 2868–2877) afforded 3′-iodide 3A. A more obvious reagent system of PPh3, I2 and imidazole was also investigated for this iodination, but necessitated the use of high temperatures at which the 4-N-benzoyl group was labile. A crystal structure obtained for 3′-iodide 3A confirmed the iodination proceeded with stereoinversion, setting the stage for base-mediated E2-elimination of HI. Accordingly, selective 5′-O-silyl cleavage effected by TFA-water, then treatment with DABCO provided 4-N-benzoyl-2′-O-TBDMS-ddhC: intermediate 5A. This intermediate formed the linchpin for the synthesis of all ddhC-based targets. The aforementioned synthetic route was also amenable to triisopropylsilyl (TIPS) or tert-butyldiphenylsilyl (TBDPS) protecting group strategies. Treatment of 4-N- benzoylcytidine (1) with triisopropylsilyl chloride afforded silyl ether 2B regioselectively. Iodination of 2B, followed by selective 5′-O-TIPS cleavage and DABCO-mediated elimination of HI afforded 4-N-benzoyl-2′-O-TIPS-ddhC (5B). Treatment of 4-N-benzoylcytidine (1) with tert-butyldiphenylsilyl chloride, meanwhile, afforded a mixture of silyl ether products from which silyl ether 2C could be isolated. Iodination, selective 5′-O-TBDPS cleavage and DABCO-mediated elimination of HI afforded 4-N-benzoyl-2′-O-TBDPS-ddhC (5C). Furthermore, the enantiomer of compound 5A, namely compound ent-5A (Scheme 2), can be prepared in an identical method to the above sequence except beginning from the N-4-L-benzoyl cytidine (ent-1) (also sourced from Biosynth Carbosynth ^® ). Monophosphorylation of alcohol 5A was first attempted by the Yoshikawa method (POCl3 in trimethylphosphate, Tetrahedron Letters 1967, 8 (50), 5065–5068). However, a complex mixture of products was obtained. Phosphoramidite chemistry was instead employed to access the monophosphate (Tetrahedron Lett. 1997, 38, 7407) delivering difluorenylmethyl phosphate 12 (Scheme 3). Both the fluorenylmethyl and N-benzoyl groups could be removed from phosphate ester 12 using ammonia in methanol to deliver free phosphate 11. Phosphorylation of the 5′-alcohol was also achieved without protection of the 4-N group. Removal of the 4-N-benzoyl group with ammonia in methanol afforded alcohol 13, which then underwent selective reaction with phosphoramidite to give phosphate ester 14. Compound 13 could be converted to the alternatively protected 4-N-DMTr-protected intermediate 15 by transient protection of the 5’-alcohol via chlorotrimethylsilane and reaction with 4,4′-dimethoxytrityl chloride. Fluorenylmethyl deprotection of compound 14 with triethylamine in acetonitrile provided free phosphate 11. Phosphate 11 was also accessed via the tert-butyl phosphate ester 9 (Synthesis 1988, 1988 (2), 142–144) as an orthogonal protecting group strategy. Treatment of phosphate ester 9 with ammonia in methanol removed the 4-N-benzoyl group selectively to give phosphate ester 10. The tert- butyl phosphate esters were cleaved by treatment with triethylamine and chlorotrimethylsilane in hot acetonitrile (Tetrahedron Letters 1991, 32 (3), 395–398) to give phosphate 11 without affecting the 2′-O-TBDMS ether. 2′-O-TBDMS-protected phosphate 11 provided access to the phosphorylated forms of ddhC; ddhCMP (16), ddhCDP (18) and ddhCTP (20) (Scheme 4). The TBDMS group of phosphate 11 underwent traceless deprotection under mild acidic conditions to give ddhCMP (16) quantitatively. ddhCMP (16) was isolated as its sodium salt following ion exchange. ddhCDP (18) and ddhCTP (20) were both prepared from monophosphate 11 using the method reported by Hoard and Ott (J. Am. Chem. Soc. 1965, 87 (8), 1785–1788). Adoption of this strategy over direct di- or triphosphorylation of alcohol 5A was motivated by the scalability of the reaction (J. Org. Chem. 1990, 55 (6), 1834–1841), as well as the simplicity of the reagent system, which would streamline purification. Activation of monophosphate 11 as the imidazolidate was performed using CDI, the excess of which was quenched using water. In situ treatment of the imidazolidate with the bistributylammonium salt of pyrophosphate gave 2’-O-TBDMS-protected triphosphate 19. When MeOH was used as a CDI quenching agent instead of water, formation of a methyl carbamate at 4-N of the cytosine nucleobase was observed. TBDMS-protected triphosphate 19 exhibits good retention on C18 silica, a feature we attribute to the lipophilic TBDMS protecting group. This enabled rapid purification of the triphosphate by reverse phase flash chromatography using a water-MeOH eluent system, whereas oligophosphates usually require purification by ion-exchange chromatography (Organophosphorus Reagents: A Practical Approach in Chemistry; The Practical Approach in Chemistry Series; Oxford University Press: Oxford, New York, 2004). Traceless TBDMS-cleavage was effected by treatment with Dowex resin in water, affording ddhCTP (20) in excellent yield. This synthesis was used to prepare 1 g of ddhCTP (20) in a single pass and therefore provides ample access to this compound for biological evaluation. ddhCDP (18) was also readily accessed from monophosphate 11 by activation with CDI, treatment with orthophosphate, and Dowex-mediated TBDMS cleavage. The same TBDMS-protecting group strategy was applied to the synthesis of ddhUMP (33) and ddhUTP (32) (Scheme 5). Scheme 5

Analogous to the synthesis of TBDMS-protected ddhC 5A, adaptation of procedures from Petrova et al. (Tetrahedron Letters, 2010, 51, 6874–6876) enabled synthesis of aldehyde 27 from uridine (21), which was sourced from AK Scientific, Inc. Isolation of pure aldehyde 27 was not possible. However, treatment of partially purified 27 with TBDMSCl and triethylamine afforded TBDMS ether 28, which was readily purified by flash column chromatography. Reduction of aldehyde 28 with sodium borohydride afforded alcohol 25. The sequence of silylation, iodination and elimination reactions which provides scalable access 2′-O-TBDMS-4-N-benzoyl ddhC (5A) has also been applied to the synthesis of 2′-O-TBDMS ddhU (25). Silylation of uridine (21) provided bis-TBDMS ether 22 (Scheme 5). Sequential Appel reaction of alcohol 22 with the triphenylphosphine-iodine-imidazole reagent system, partial TBDMS cleavage with TFA-water, then DABCO-mediated elimination of HI all proceeded to afford 2′-O-TBDMS ddhU (25). ddhUMP (31) was accessible from alcohol 25 via fluorenylmethyl phosphate 29. Cleavage of the phosphate esters using triethylamine in acetonitrile afforded free phosphate 30 as the triethylamine salt. Traceless deprotection of the TBDMS group was achieved using Dowex resin (H form) as an acid catalyst in water, affording ddhUMP (31) quantitatively. ddhUTP (33) was accessed from TBDMS-protected monophosphate 30 by preparation of the imidazolidate using CDI, treatment with pyrophosphate tributylammonium salt to give triphosphate 32, then TBDMS cleavage using Dowex resin (H form) in water. Treatment of compound 23 with DABCO afforded alkene 34 (Scheme 6) which could then be converted to the N-hydroxy compound 35 by reaction with 2,4,6- triisopropylbenzenesulfonyl chloride followed by hydroxylamine hydrochloride. Deprotection of both TBDMS-protecting groups to afford N-4-hydroxy-ddhC (36) could be accomplished by triethylamine-HF complex in THF. The sequence of silylation, iodination and elimination reactions which provides scalable access to 2′-O-TBDMS-4-N-benzoyl ddhC (5A) has also been applied to the synthesis of 2′-O-TBDMS-2-N-isobutyryl ddhG (41) (Scheme 7). Silyl protection of 2-N- isobutyrylguanosine (37), which was sourced from Biosynth Carbosynth ^® , provided bis- TBDMS ether 38. Appel reaction of alcohol 38 to afford iodide 39 can be achieved with either a triphenylphosphine-iodine-imidazole reagent system, or triphenoxy methylphosphonium iodide. Selective 5′-O-TBDMS cleavage of iodide 39 with TFA-H ₂ O, then DABCO-mediated elimination of HI afforded 2′-O-TBDMS-2-N-isobutyryl ddhG (41). ddhGTP (44) was accessed from alcohol 41 via fluorenylmethyl phosphate ester 42. Base-mediated cleavage of O-fluorenylmethyl and N-isobutyroyl groups provided 2’- OTBDMS-protected monophosphate 43. Phosphate 43 was converted to ddhGTP (44) by treatment with CDI and pyrophosphate tributylammonium salt. The 2’-OTBDMS group was cleaved during handling of the triphosphate prior to purification, affording ddhGTP (44) directly from TBDMS-protected compound 43 in a single step.

The sequence of silylation, selective dimethoxytritylation, iodination, deprotection and elimination reactions provides access to 2′-O-TBDMS-5-aza-ddhC (50) (Scheme 8). Silyl protection of 5-aza cytidine (45), which was sourced from Biosynth Carbosynth ^® , provided bis-TBDMS ether 46. Dimethoxytritylation of bis-TBDMS ether 46 afforded alcohol 47. Appel reaction of alcohol 47 to afford iodide 48 can be achieved with a triphenylphosphine-iodine-imidazole reagent system. Selective 5′-O-TBDMS cleavage of iodide 48 with TFA-H ₂ O with concomitant dimethoxytrityl cleavage, then DABCO-mediated elimination of HI afforded 2′-O-TBDMS-5-aza-ddhC (50). Subsequent deprotection of the 2′-O-TBDMS protecting group with ammonium fluoride in methanol provides access to 5- aza-ddhC (51). The 5-fluorouridine analogue 56 (Scheme 9) was prepared from known compound 4- N-benzoyl-5-fluorocytidine (52) (Nucleic Acids Research, 2009, 37(22), 7728-7740) by a similar method to that which furnished the 2’-O-TBDMS-N-4-Benzoyl-ddhC intermediate 5A. Selective 2’,5’-bis-silyl ether protection followed by iodination afforded compound 54. However, in this instance, upon treatment of iodide 54 with TFA/water, uridine compound 55 was unexpectedly obtained, where the 5-fluoro-cytosine base moiety underwent hydrolysis to the 5-fluoro-uracil base moiety. Compound 55 could be converted to 2’-O- TBDMS-protected 5-fluoro-ddhU compound 56 by DABCO-mediated elimination.

The synthetic route utilising a 2′-O-TBDMS protected ddhC derivative enables the facile synthesis of biologically-relevant phosphates of ddhC. The silyl group protection strategy also has the benefit of providing a lipophilic handle that enables reverse phase flash chromatographic purification of highly charged compounds that would otherwise require more intensive purification methods. Further, this route enables the TBDMS protecting group to be removed without trace under mild conditions to provide the deprotected targets in good purity. Taken together, these properties have facilitated a robust and scalable synthesis of ddhCTP (20), and similar compounds, providing useful quantities of antiviral metabolites and their prodrugs for biological studies. As shown by the applicant, the synthetic methodology is applicable not only to 3’- deoxy-3’,4’-didehydrocytidines, but also to 3’-deoxy-3’,4’-didehydrouridines and 3’-deoxy- 3’,4’-didehydroguanidines. The methodology may be used for the synthesis of 3’-deoxy- 3’,4’-didehydroribonucleosides in general. The chemical synthesis route developed by the applicant has led to a novel class of compounds useful as intermediates for the synthesis of a wide range of 3’-deoxy-3’,4’-didehydroribonucleoside based antiviral drugs. **** Any reference to prior art documents in this specification is not to be considered an admission that such prior art is widely known or forms part of the common general knowledge in the field. The invention is further described with reference to the following Examples. It will be appreciated that the invention as claimed is not intended to be limited in any way by these Examples. EXAMPLES Example 1: 4-N-Benzoyl-2′,5′-bis-O-(tert-butyldimethylsilyl)cytidin e (2A) The title compound was prepared according to a literature procedure (Can. J. Chem. 1978, 56, 2768–2780). To a suspension of 4-N-benzoylcytidine (1) (10.0 g, 28.8 mmol) in anhydrous pyridine (58 mL) at room temperature was added tert-butyldimethylsilyl chloride (13.4 g, 86.2 mmol). The reaction mixture was stirred for 3 d, then concentrated in vacuo. The resultant oil was dissolved in CHCl ₃ (150 mL) and washed with 0.5 M aq. HCl (50 mL). The aqueous layer was back-extracted with CHCl ₃ (50 mL), then the combined organic layers were washed with water (40 mL), brine (40 mL), dried over anhydrous MgSO ₄ , filtered and concentrated in vacuo. Purification by flash column chromatography (9 × 15 cm silica gel, 20%–60% EtOAc-Hex) afforded the title compound (11.5 g, 69% yield) as a colourless foam. ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.67–8.57 (m, 1H), 8.53 (d, J = 4.4 Hz, 1H), 7.90 (d, J = 5.4 Hz, 2H), 7.63–7.59 (m, 1H), 7.54–7.49 (m, 2H), 5.98 (d, J = 2.2 Hz, 1H), 4.24 (dd, J = 4.6, 2.2 Hz, 1H), 4.19–4.05 (m, 3H), 3.91–3.87 (m, 1H), 2.45 (d, J = 8.4 Hz, 1H), 0.97 (s, 9H), 0.94 (s, 9H), 0.28 (s, 3H), 0.17 (s, 3H), 0.16 (s, 3H), 0.16 (s, 3H). Example 2: 1-(2′,5′-Bis-O-(tert-butyldimethylsilyl)-3′-iodo-β-D- threo- pentofuranosyl)-4-N-benzoylcytosine (3A) A flask was charged with methyltriphenoxyphosphonium iodide (6.41 g, 11.3 mmol) under argon, followed by 2′,5′-bis-O-(tert-butyldimethylsilyl)-4-N-benzoylcytidin e (2A) (4.35 g, 7.55 mmol). The solids were dissolved in DMF (50 mL), then pyridine (1.25 mL, 15.4 mmol) was added and the reaction mixture was stirred at room temperature for 18 h. The reaction mixture was quenched by addition of Et ₃ N (5 mL) and MeOH (5 mL), then stirred for 10 min. The reaction mixture was partitioned between water (500 mL) and EtOAc (50 mL), then the aqueous layer was extracted with EtOAc (2 × 50 mL). The combined organic layers were washed with brine (25 mL), dried over anhydrous MgSO ₄ , filtered and concentrated in vacuo. The crude oil was purified by flash column chromatography (silica gel, 10–30% EtOAc-Hex) to afford the title compound (3.38 g, 65%) as an off-white solid. Alternatively, the worked-up crude reaction mixture can be recrystallised from methanol at between 40-60 ℃. ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.23 (d, J = 7.5 Hz, 1H), 7.89 (d, J = 7.8 Hz, 2H), 7.60 (t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.7 Hz, 3H), 5.75 (d, J = 1.7 Hz, 1H), 4.79 (t, J = 1.8 Hz, 1H), 4.13 (dd, J = 4.1, 1.8 Hz, 1H), 4.07–3.99 (m, 2H), 3.82 (dd, J = 10.3, 5.1 Hz, 1H), 0.94 (s, 9H), 0.92 (s, 9H), 0.20 (s, 3H), 0.16 (s, 6H), 0.14 (s, 3H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 166.3, 162.4, 154.6, 145.3, 133.3, 129.2, 127.7, 95.7, 93.7, 83.8, 81.9, 68.0, 30.5, 26.0, 25.8, 18.5, 18.0, −4.6, −4.8, −5.0, −5.1; HRMS (ESI+): Calculated for C ₂₈ H ₄ 5N ₃ O ₅ Si ₂ I: 686.1942. Found [M + H] ⁺ : 686.1950. Example 3: 1-(2′-O-(tert-Butyldimethylsilyl)-3′-iodo-β-D-threo-pen tofuranosyl)-4- N-benzoylcytosine (4A) To a solution of 1-(2′,5′-bis-O-(tert-butyldimethylsilyl)-3′-iodo-β-D- threo- pentofuranosyl)-4-N-benzoylcytosine (3A) (5.64 g, 8.23 mmol) in THF (24 mL) at 0 ℃ was added a mixture of TFA-H ₂ O (1:1, 7.2 mL) dropwise over 3 min. The reaction mixture was warmed to room temperature and stirred for 3.5 h. The reaction was neutralised by addition of sat aq NaHCO ₃ (50 mL), then extracted with EtOAc (3 × 50 mL). The combined organic layers were washed with sat aq NaHCO ₃ (20 mL), brine (20 mL), dried over anhydrous MgSO ₄ , filtered and concentrated in vacuo. The crude oil was purified by flash column chromatography (120 g silica gel, 10%–100% EtOAc-Hex) afforded the title compound (4.17 g, 89% yield) as a colourless solid. Alternatively, the worked-up crude reaction mixture can be recrystallised by suspending and stirring in 5% EtOAc in petroleum ether (60-80) (at a volume equivalent to around 2 mL/g of the starting material 3A used) followed by addition of CHCl ₃ (at a volume equivalent to around 0.4-0.7 mL/g of starting material 3A) at 40-50 ℃. ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.92 (s, 1H), 8.20 (d, J = 7.6 Hz, 1H), 7.89 (d, J = 8.7 Hz, 2H), 7.62–7.47 (m, 4H), 5.67 (d, J = 1.5 Hz, 1H), 4.88 (t, J = 1.7 Hz, 1H), 4.18–4.04 (m, 3H), 3.88 (dd, J = 11.7, 4.3 Hz, 1H), 0.91 (s, 9H), 0.20 (s, 3H), 0.16 (s, 3H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 166.6, 162.7, 155.1, 145.7, 133.3, 129.2, 127.7, 96.0, 94.6, 83.7, 82.0, 68.0, 29.3, 25.8, 18.0, −4.6, −4.8; HRMS (ESI+): Calculated for C ₂₂ H ₃₁ N ₃ O ₅ SiI: 572.1078. Found [M + H] ⁺ : 572.1084. Example 4: 4-N-Benzoyl-2′-O-(tert-butyldimethylsilyl)-3′-deoxy-3′ ,4′-didehydro- cytidine (5A) To a suspension of 1-(2′-O-(tert-butyldimethylsilyl)-3′-iodo-β-D-threo- pentofuranosyl)-4-N-benzoylcytosine (4A) (2.75 g, 4.81 mmol) in PhMe (96 mL) was added DABCO (1.91 g, 16.8 mmol) and the resulting suspension was heated to 75 ℃ and stirred for 18 h. The reaction mixture was cooled to room temperature and filtered to remove precipitated salts, then the filtrate was concentrated in vacuo. The crude product was purified by flash column chromatography (80 g silica gel, 40%–100% EtOAc-Hex) to afford the title compound (2.00 g, 94% yield) as a colourless solid. ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.72 (s, 1H), 7.94–7.81 (m, 2H), 7.68–7.57 (m, 2H), 7.56–7.42 (m, 3H), 6.36 (d, J = 1.5 Hz, 1H), 5.21 (d, J = 2.4 Hz, 1H), 4.86 (br s, 1H), 4.41–4.30 (m, 2H), 0.90 (s, 9H,), 0.16 (s, 3H), 0.11 (s, 3H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 166.9, 162.8, 161.4, 154.9, 143.8, 133.2, 133.0, 129.0, 127.8, 101.5, 97.3, 94.3, 80.8, 57.4, 25.8, 18.2, −4.5, −4.7; HRMS (ESI+): Calculated for C ₂₂ H ₃₀ N ₃ O ₅ Si: 444.1955. Found [M + H] ⁺ : 444.1953. Example 5: 2′,5′-Bis-O-(triisopropylsilyl)-4-N-benzoylcytidine (2B) The title compound was prepared according to a literature procedure (Tetrahedron Lett. 1974, 15(33), 2861–2863). To a suspension of 4-N-benzoylcytidine (1) (2.0 g, 5.8 mmol) and imidazole (2.00 g, 29.1 mmol) in anhydrous DMF (6 mL) at room temperature was added triisopropylsilyl chloride (3.20 mL, 14.4 mmol). The reaction mixture was stirred for 24 h, then partitioned between EtOAc (50 mL) and saturated aq. NH ₄ Cl (50 mL). The aqueous layer was extracted with EtOAc (50 mL). The combined organic layers were washed with water (50 mL), brine (50 mL), dried over anhydrous MgSO ₄ , filtered and concentrated in vacuo. The crude oil was purified by flash column chromatography (silica gel, 0–30% EtOAc-Hex) to afford the title compound (2.2 g, 58% yield) as a colourless foam. ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.86–8.59 (m, 1H), 8.50 (d, J = 7.4 Hz, 1H), 7.89 (d, J = 7.6 Hz, 2H), 7.58 (t, J = 7.4 Hz, 1H), 7.49 (t, J = 7.7 Hz, 2H), 7.46–7.27 (m, 1H), 6.02 (d, J = 2.1 Hz, 1H), 4.37 (dd, J = 4.4, 2.4 Hz, 1H), 4.33–4.22 (m, 1H), 4.17 (dd, J = 11.6, 1.5 Hz, 2H), 4.13–4.04 (m, 1H), 3.96 (dd, J = 11.6, 1.3 Hz, 1H), 2.59 (d, J = 8.2 Hz, 1H), 1.34–1.15 (m, 6H), 1.14–1.05 (m, 36H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 166.5, 162.2, 154.7, 145.0, 133.2, 129.1, 127.7, 96.2, 90.3, 84.7, 76.9, 69.0, 61.7, 18.12, 18.06, 12.3, 11.9; HRMS (ESI+): Calculated for C ₃₄ H ₅₈ N ₃ O ₆ Si ₂ : 660.3859. Found [M + H] ⁺ : 660.3853. Example 6: 1-(2′,5′-Bis-O-(triisopropylsilyl)-3′-iodo-β- ^D -threo-pentofuranosyl)-4- N-benzoylcytosine (3B) A flask was charged with methyltriphenoxyphosphonium iodide (520 mg, 1.15 mmol) under argon, followed by 2′,5′-bis-O-(triisopropylsilyl)-4-N-benzoylcytidine (2B) (500 mg, 0.758 mmol). The solids were dissolved in DMF (5 mL), then pyridine (0.125 mL, 1.54 mmol) was added and the reaction mixture was stirred at room temperature for 18 h. The reaction mixture was quenched by addition of Et ₃ N (1 mL) and MeOH (1 mL), then stirred for 10 min. The reaction mixture was partitioned between 10% aq Na ₂ S ₂ O ₃ (50 mL) and EtOAc (50 mL). The aqueous layer was extracted with EtOAc (2 × 50 mL). The combined organic layers were washed with brine (25 mL), dried over anhydrous MgSO ₄ , filtered and concentrated in vacuo. The crude oil was purified by flash column chromatography (silica gel, 5–20% acetone-Hex) to afford the title compound (290 mg, 50%) as a white solid. ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.72–8.49 (m, 1H), 8.21 (d, J = 7.5 Hz, 1H), 7.88 (d, J = 7.5 Hz, 2H), 7.67–7.47 (m, 4H), 5.81–5.70 (m, 1H), 5.07–4.94 (m, 1H), 4.21 (d, J = 3.6 Hz, 1H), 4.18 (dd, J = 10.1, 5.5 Hz, 1H), 4.04–3.96 (m, 1H), 3.86 (dd, J = 10.0, 6.6 Hz, 1H), 1.28–1.07 (m, 42H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 162.4, 133.3, 129.2, 127.6, 95.3, 95.0, 84.1, 82.4, 68.2, 32.4, 18.14, 18.10, 12.3, 12.1 ( ¹³ C signals for the nucleobase and Bz carbonyl carbon nuclei were too weak to be observed); HRMS (ESI+): Calculated for C ₃₄ H ₅₇ IN ₃ O ₅ Si ₂ : 770.2876. Found [M + H] ⁺ : 770.2883. Example 7: 1-(2′-O-(Triisopropylsilyl)-3′-iodo-β-D-threo-pentofura nosyl)-4-N- benzoylcytosine (4B) To a solution of 1-(2′,5′-bis-O-(triisopropylsilyl)-3′-iodo-β-D-threo- pentofuranosyl)- 4-N-benzoylcytosine (3B) (200 mg, 0.260 mmol) in THF (12 mL) at 0 °C was added a mixture of TFA-H ₂ O (1:1, 6 mL) dropwise over 3 min. The reaction mixture was warmed to room temperature and stirred for 10 h. The reaction was neutralised by addition of sat aq NaHCO ₃ (50 mL), then extracted with EtOAc (3 × 50 mL). The combined organic layers were washed with sat aq NaHCO ₃ (20 mL), brine (20 mL), dried over anhydrous MgSO ₄ , filtered and concentrated in vacuo. The crude oil was purified by flash column chromatography (silica gel, 10–50% EtOAc-Hex) to afford the title compound (146 mg, 92% yield) as a colourless solid. ¹ H NMR (500 MHz, CDCl ₃ ) δ 9.03–8.62 (m, 1H), 8.22 (d, J = 7.6 Hz, 1H), 7.89 (d, J = 7.7 Hz, 2H), 7.74–7.42 (m, 4H), 5.77–5.70 (m, 1H), 5.06–5.00 (m, 1H), 4.23–4.12 (m, 2H), 4.12–4.02 (m, 1H), 3.93–3.79 (m, 1H), 1.32–1.14 (m, 3H), 1.17–1.02 (m, 18H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 162.6, 145.6, 133.3, 129.2, 127.7, 95.0, 84.2, 82.3, 68.2, 30.0, 18.2 ( ¹³ C signals for the nucleobase and Bz carbonyl carbon nuclei were too weak to be observed); HRMS (ESI+): Calculated for C ₂₅ H ₃₇ IN ₃ O ₅ Si: 614.1542. Found [M + H] ⁺ : 614.1536. Example 8: 4-N-Benzoyl-2′-O-(triisopropylsilyl)-3′-deoxy-3′,4′- didehydrocytidine (5B) To a suspension of 1-(2′-O-(triisopropylsilyl)-3′-iodo-β-D-threo-pentofura nosyl)-4-N- benzoylcytosine (4B) (108 mg, 0.176 mmol) in PhMe (3 mL) was added DABCO (70 mg, 0.59 mmol) and the resulting suspension was heated to 75 °C and stirred for 5 h. The reaction mixture was cooled to room temperature, then partitioned between 1 M aq Na ₂ S ₂ O ₃ (20 mL) and EtOAc (20 mL). The aqueous layer was extracted with EtOAc (2 × 20 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous MgSO ₄ , filtered and concentrated in vacuo. The crude product was purified by flash column chromatography (silica gel, 10–50% EtOAc-Hex) to afford the title compound (62 mg, 73% yield) as a colourless solid. ¹ H NMR (500 M _H z, CDCl ₃ ) δ 9.60–8.82 (m, 1H), 7.85 (d, J = 7.6 Hz, 2H), 7.62 (d, J = 7.5 Hz, 1H), 7.56 (t, J = 7.4 Hz, 1H), 7.45 (t, J = 7.7 Hz, 3H), 6.40 (d, J = 1.6 Hz, 1H), 5.24 (d, J = 2.4 Hz, 1H), 4.99 (t, J = 2.1 Hz, 1H), 4.39–4.25 (m, 2H), 1.12–0.96 (m, 21H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 166.8, 162.8, 161.5, 154.8, 144.2, 133.3, 132.9, 129.0, 127.9, 101.5, 97.5, 94.8, 80.7, 57.6, 18.02, 18.00, 12.2; HRMS (ESI+): Calculated for C ₂₅ H ₃₅ N ₃ NaO ₅ Si: 508.2238. Found [M + Na] ⁺ : 508.2245. Example 9: 2′,5′-Bis-O-tert-butyldiphenylsilyl-4-N-benzoylcytidine (2C) To a suspension of 4-N-benzoylcytidine (1) (1.50 g, 4.32 mmol) in pyridine (8.6 mL) was added TBDPSCl (3.2 mL, 11.9 mmol) and the reaction mixture was stirred at room temperature for 18 h, then heated to 50 °C and stirred for another 24 h. The reaction was treated with further TBDPSCl (1.2 mL, 4.5 mmol), stirred at 60 °C for 6 h, then cooled to room temperature and concentrated in vacuo. The crude residue was partitioned between EtOAc (100 mL) and 1 M aq HCl (30 mL). The organic layer was washed with 1 M aq HCl (30 mL), water (30 mL), brine (30 mL), dried over anhydrous MgSO ₄ , filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (10–100% EtOAc-Hex) to afford the title compound (948 mg, 27% yield) as a colourless foam. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.98 (d, J = 7.6 Hz, 2H), 7.70 (d, J = 7.6 Hz, 1H), 7.66– 7.48 (m, 11H), 7.48–7.22 (m, 13H), 6.36 (d, J = 5.8 Hz, 1H), 4.41 (t, J = 5.5 Hz, 1H), 4.29 (dt, J = 5.2, 2.7 Hz, 1H), 4.20 (q, J = 2.3 Hz, 1H), 3.86 (ddd, J = 72.5, 11.8, 2.2 Hz, 2H), 2.97 (brs, 1H), 1.12 (s, 9H), 0.96 (s, 9H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 161.8, 144.0, 135.9, 135.63, 135.61, 135.4, 133.2, 132.60, 132.57, 132.1, 131.6, 130.4, 130.2, 130.1, 129.0, 128.2, 128.13, 128.06, 128.0, 97.6, 88.6, 85.3, 77.0, 71.5, 64.1, 27.03, 27.00, 19.2 ( ¹³ C signals for the nucleobase and Bz carbonyl carbon nuclei were too weak to be observed); HRMS (ESI/Q-TOF) m/z [M + H] ⁺ Calcd for C ₄₈ H ₅₄ N ₃ O ₆ Si ₂ : 824.3551; Found 824.3544. Example 10: 1-(2′,5′-Bis-O-(tert-butyldiphenylsilyl)-3′-iodo-β-D- threo- pentofuranosyl)-4-N-benzoylcytosine (3C) 2′,5′-Bis-O-tert-butyldiphenylsilyl-4-N-benzoylcytidine (2C) (540 mg, 0.655 mmol) and methyltriphenoxyphosphonium iodide (581 mg, 1.03 mmol) were dissolved in DMF (4.5 mL) and treated with pyridine (0.11 mL, 1.4 mmol). The reaction mixture was stirred at room temperature for 22 h, then quenched by addition of MeOH (1 mL) and Et ₃ N (0.1 mL), stirred for 30 min then partitioned between EtOAc (20 mL) and water (50 mL). The aqueous layer was extracted with EtOAc (15 mL), then the combined organic layers were washed with 10% aq Na ₂ S ₂ O ₃ (5 mL), brine (2 × 10 mL), dried over anhydrous MgSO ₄ , filtered and concentrated in vacuo. Purification by flash column chromatography on silica gel (0–40% EtOAc-Hex) afforded the title compound (183 mg, 30% yield) as a colourless foam. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.95–7.87 (m, 3H), 7.83–7.78 (m, 2H), 7.75– 7.67 (m, 6H), 7.62–7.56 (m, 1H), 7.53–7.37 (m, 15H), 6.02 (d, J = 0.8 Hz, 1H), 4.85 (s, 1H), 4.08 (td, J = 5.9, 3.6 Hz, 1H), 4.00 (dd, J = 10.5, 5.8 Hz, 1H), 3.88 (d, J = 3.7 Hz, 1H), 3.74 (dd, J = 10.5, 5.9 Hz, 1H), 1.19 (s, 9H), 1.07 (s, 9H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 162.3, 145.4, 136.3, 135.7, 133.7, 133.2, 133.0, 132.9, 131.7, 130.30, 130.28, 130.1, 130.0, 129.1, 128.2, 128.0, 127.95, 127.90, 127.7, 95.6, 94.6, 85.0, 81.7, 68.6, 31.1, 27.0, 26.9, 19.3 ( ¹³ C signals for the nucleobase and Bz carbonyl carbon nuclei were too weak to be observed); HRMS (ESI/Q-TOF) m/z [M + H] ⁺ Calcd for C ₄₈ H ₅₃ IN ₃ O ₅ Si ₂ : 934.2568; Found 934.2560. Example 11: 1-(2′-O-(tert-Butyldiphenylsilyl)-3′-iodo-β-D-threo-pen tofuranosyl)- 4-N-benzoylcytosine (4C) To a solution of 1-(2′,5′-bis-O-(tert-butyldiphenylsilyl)-3′-iodo-β-D- threo- pentofuranosyl)-4-N-benzoylcytosine (3C) (166 mg, 0.178 mmol) in MeCN (0.9 mL) was added TfOH-SiO ₂ (2 mmol/g TfOH on silica gel, 150 mg, 0.30 mmol) prepared according to Carbohyd. Res. 2012, 354, 6–20. The resulting slurry was stirred at 50 °C for 4 h, then cooled to room temperature and filtered through cotton wool, and the silica gel was washed with EtOAc (5 mL). The filtrate was diluted with EtOAc (10 mL) and washed with sat aq NaHCO ₃ (5 mL), then the aqueous layer was back-extracted with EtOAc (10 mL). The combined organic layers were washed with brine (5 mL), dried over anhydrous MgSO ₄ , filtered and concentrated in vacuo. Purification by flash chromatography on silica gel (10– 100% EtOAc-Hex) afforded the title compound (40 mg, 32% yield) as a colourless solid. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.85 (s, 1H), 8.06 (d, J = 7.6 Hz, 1H), 7.89 (d, J = 7.7 Hz, 2H), 7.74 (dd, J = 7.4, 2.0 Hz, 2H), 7.67 (dt, J = 6.6, 1.6 Hz, 2H), 7.63–7.54 (m, 1H), 7.54– 7.31 (m, 9H), 6.03 (d, J = 1.5 Hz, 1H), 4.85 (d, J = 1.5 Hz, 1H), 4.13 (dt, J = 6.5, 4.2 Hz, 1H), 3.95 (dd, J = 11.9, 6.5 Hz, 1H), 3.89 (dd, J = 4.3, 1.2 Hz, 1H), 3.72 (dd, J = 11.9, 4.1 Hz, 1H), 2.08 (s, 1H), 1.13 (s, 9H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 162.5, 145.6, 136.2, 135.8, 133.4, 133.3, 131.7, 130.38, 130.35, 129.1, 128.2, 128.1, 127.7, 96.0, 94.4, 85.0, 81.6, 68.1, 29.3, 27.0, 19.3 ( ¹³ C signals for the nucleobase and Bz carbonyl carbon nuclei were too weak to be observed); HRMS (ESI/Q-TOF) m/z [M + H] ⁺ Calcd for C ₃₂ H ₃₅ IN ₃ O ₅ Si: 696.1391; Found 696.1399. Example 12: 1-(2′-O-(tert-Butyldiphenylsilyl)-3′-deoxy-3′,4′-did ehydro-4-N- benzoylcytosine (5C) To a solution of 1-(2′-O-(tert-butyldiphenylsilyl)-3′-iodo-β-D-threo-pen tofuranosyl)- 4-N-benzoylcytosine (4C) (39 mg, 0.056 mmol) in PhMe (1.1 mL) was added DABCO (23 mg, 0.20 mmol) and the reaction mixture was heated to 70 °C for 5 h, then 80 °C for 1 h. The reaction mixture was cooled to room temperature, concentrated in vacuo and the resultant residue was purified by flash column chromatography on silica gel (10−80% EtOAc-Hex) to afford the title compound (27 mg, 83% yield) as a colourless solid. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.89–7.82 (m, 2H), 7.67 (ddd, J = 8.0, 5.1, 1.7 Hz, 4H), 7.61–7.55 (m, 1H), 7.47 (dd, J = 8.3, 7.1 Hz, 2H), 7.43–7.30 (m, 8H), 6.59 (d, J = 2.0 Hz, 1H), 4.94 (t, J = 2.3 Hz, 1H), 4.90 (d, J = 2.4 Hz, 1H), 4.26–4.11 (m, 2H), 1.07 (s, 9H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 162.5, 161.5, 143.9, 136.0, 135.8, 133.8, 133.4, 132.9, 130.1, 130.0, 129.1, 128.0, 127.8, 101.0, 97.5, 94.6, 81.5, 57.7, 26.9, 19.2 ( ¹³ C signals for the nucleobase and Bz carbonyl carbon nuclei were too weak to be observed); HRMS (ESI/Q- TOF) m/z [M + H] ⁺ Calcd for C ₃₂ H ₃₄ N ₃ O ₅ Si: 568.2268; Found 568.2275. Example 13: 4-N-Benzoyl-2’,3’-O-methoxymethylidenecytidine (6) 4-N-Benzoylcytidine (1) (10.7 g, 30.2 mmol) was suspended in dry DMF (100 mL) and trimethyl orthoformate (130 mL) before PTSA (250 mg, 1.3 mmol) was added. The mixture was stirred for 24 h at r.t. After the reaction had consumed all starting material an excess of Amberlyst® A-21 resin was added and the mixture stirred for 15 mins before filtering. Triethylamine (5 mL) was added to the filtrate before concentrating to dryness using high vacuum at 50 °C. Toluene (250 mL) was added to the crude and the suspension was concentrated again. Toluene was added and concentrated twice more before the crude was suspended in ethyl acetate and brought to 70 °C for ca. 30 mins. After cooling to 15 °C the solution was allowed to stir for 20 mins before the first crop of white precipitate was collected by filtration, and washing with cold ethyl acetate. On standing (24-40 h), more product precipitated from the mother-liquor as a white solid and was collected by filtration, washing with cold ethyl acetate. The overall yield for the three crops isolated was 89% (10.4 g). The white, solid product was a mixture of epimers at the orthoformate stereocentre in the proportion ca. 3.3 : 1. It was possible to fully assign NMR data for the major (A) and minor (B) components on this mixture. ¹ H NMR (500 MHz, DMSO-d6); δ 11.26 (s, 1H _A+B , NH), 8.28 (t, J = 7.6 Hz, 1H _A+B , H6-Cyt), 8.08–7.95 (m, 2H _A+B , o-PhH), 7.71–7.59 (m, 1H _A+B , p-PhH), 7.52 (t, J = 7.8 Hz, 2H _A+B , m-PhH), 7.41–7.29 (m, 1H _A+B , H5- Cyt), 6.12 (s, 1HB, HC(CH ₃ )(OR) ₂ ), 6.02 (s, 1HA, HC(CH ₃ )(OR) ₂ ), 5.99 (d, J = 2.5 Hz, 1HA, H1’), 5.87 (d, J = 2.1 Hz, 1H _B , H1’), 5.18-5.06 (m, 1H _A+B , OH), 5.04 (dd, J = 7.2, 2.4 Hz, 1H _A+B , H2’), 4.91 (dd, J = 6.3, 3.4 Hz, 1HB, H3’), 4.85 (dd, J = 7.1, 3.5 Hz, 1HA, H3’), 4.34 (q, J = 4.4 Hz, 1HA, H ₄ ’), 4.24 (q, J = 4.2 Hz, 1HB, H ₄ ’), 3.76–3.59 (m, 2H _A+B , H5’(CH2)), 3.34 (s, 3HA, OCH3), 3.24 (s, 1HB, OCH3); ¹³ C NMR (126 MHz, DMSO) δ 167.33 (Q), 163.50 (Q), 154.35 (Q), 146.89 (A; C6-Cyt), 146.67 B; C6-Cyt), 133.07 (Q), 132.72 (A and B; o- PhC), 128.43 and 128.40 (A and B; p-PhC and m-PhC), 118.05 (A; HC(OCH ₃ )(OR ₂ )), 116.72 (B; HC(OCH ₃ )(OR ₂ )), 96.09 and 96.03 (A and B; C5-Cyt), 94.30 (A; C1’), 93.42 (B; C1’), 88.07 (A; C4’), 86.94 (B; C4’), 84.46 (A; C2’), 83.83 (B; C2’), 80.83 (A; C3’), 80.21 (B; C3’), 61.47 (A; C5’), 61.10 (B; C5’), 51.70 (A; OCH3), 50.30 (B; OCH3). Example 14: 4-N-Benzoyl-3’-deoxy-3’,4’-didehydrocytidine-5’-alde hyde (7) Following the procedure reported by Petrová et al. (Tetrahedron Letters 51 (2010) 6874-6876), 4-N-benzoyl-2’,3’-O-methoxymethylidenecytidine (6) (3.30 g, 8.47 mmol) was converted to the crude then semi-purified by column chromatography by dry loading and eluting with a gradient from 5-10% MeOH in CHCl ₃ . Fractions containing product were concentrated to dryness and triturated with boiling hot ethyl acetate, cooled in an ice bath and filtered to afford compound 7 as an off-white solid (1.30 g, 47%). ¹ H NMR (500 MHz, DMSO-d6) δ 11.33 (s, 1H), 9.57 (s, 1H), 8.08–7.91 (m, 3H), 7.69–7.58 (m, 1H), 7.57–7.46 (m, 2H), 7.34 (s, 1H), 6.51 (d, J = 2.8 Hz, 1H), 6.23 (d, J = 3.3 Hz, 1H), 6.15 (d, J = 6.6 Hz, 1H), 5.46 – 5.00 (m, 1H); ¹³ C NMR (126 MHz, DMSO) δ 183.34, 167.32, 163.61, 155.61, 153.97, 146.35, 132.99, 132.81, 128.48, 128.43, 121.63, 96.91, 96.05, 77.05; LRMS (LCMS) ESI ⁺ m/z 360.1 (M+Na ⁺ , 100%). Example 15: 4-N-Benzoyl-2’-O-tert-butyldimethylsilyl-3’-deoxy-3’,4 ’- didehydrocytidine-5’-aldehyde (8) 4-N-Benzoyl-3’-deoxy-3’,4’-didehydrocytidine-5’-alde hyde (7) (400 mg, 1.22 mmol) and imidazole (170 mg, 2.44 mmol) were dissolved in dry DMF (10 mL) before TBDMSCl (250 mg, 1.61 mmol) was added at r.t. The mixture was stirred for 3 h before more TBDMSCl (80 mg, 0.51 mmol) was added. The mixture was stirred for a further 2 h before a few drops of water were added and the mixture stirred for 20 minutes. Water and ethyl acetate were added and the aqueous was extracted with ethyl acetate before the combined organics were washed once with water, then brine and dried over MgSO ₄ and concentrated to dryness. To the residue was added toluene (20 mL) and the toluene solution was concentrated to dryness to remove residual DMF; this process was repeated three times before the crude was purified by column chromatography over silica gel, eluting with a gradient from 0-5% MeOH in CHCl ₃ to afford aldehyde 8 (528 mg, 98%). ¹ H NMR (500 MHz, Chloroform-d) δ 9.47 (s, 1H), 8.86 (br s, 1H), 7.83–7.70 (m, 2H), 7.50–7.44 (m, 1H), 7.44–7.31 (m, 4H), 6.05 (d, J = 2.5 Hz, 1H), 6.04 (d, J = 2.8 Hz, 1H), 5.15 (t, J = 2.6 Hz, 1H), 0.78 (s, 9H), 0.04 (s, 3H), 0.00 (s, 3H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 181.58, 166.77, 162.90, 156.10, 154.14, 144.45, 133.29, 132.91, 129.01, 127.72, 119.46, 97.24, 79.23, 25.65, 18.00, −4.62, −4.80; HRMS (ESI+): Calculated for C ₂₂ H ₂₈ N ₃ O ₅ Si: 442.1798. Found [M + H] ⁺ : 442.1797. Example 16: 4-N-Benzoyl-2’-O-tert-butyldimethylsilyl-3’-deoxy-3’,4 ’- didehydrocytidine (5A) 4-N-Benzoyl-2’-O-tert-butyldimethylsilyl-3’-deoxy-3’,4 ’-didehydrocytidine-5’- aldehyde (8) (400 mg, 0.91 mmol) was dissolved in methanol (10 mL) and cooled to 0 °C before sodium borohydride (35 mg, 0.91 mmol) was added. After 10 mins, and all starting material had been consumed, acetone (0.2 mL) was added. After 5 mins silica gel (1 g) was added and the mixture was concentrated to dryness. The crude product was filtered through a plug of silica eluting with 5% MeOH in CHCl ₃ . After concentration the residue was purified by column chromatography over silica gel eluting with a gradient from 0-9% MeOH in CHCl ₃ to afford alcohol 5A (265 mg, 66%) as a colourless foam. ¹ H NMR (500 MHz, Chloroform-d) δ 9.01 (s, 1H), 7.90–7.84 (m, 2H), 7.64 (d, J = 7.5 Hz, 1H), 7.61–7.55 (m, 1H), 7.52–7.44 (m, 3H), 6.36 (d, J = 1.6 Hz, 1H), 5.23–5.15 (m, 1H), 4.85 (m, 1H), 4.43–4.28 (m, 2H), 0.89 (s, 9H), 0.14 (s, 3H), 0.09 (s, 3H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 166.57, 162.61, 161.11, 154.71, 143.66, 133.22, 128.98, 127.72, 101.44, 97.12, 94.38, 80.72, 57.58, 25.75, 18.11, −4.55, −4.81; HRMS (ESI+): Calculated for C ₂₂ H ₃₀ N ₃ O ₅ Si: 444.1955. Found [M + H] ⁺ : 444.1953. Example 17: 4-N-Benzoyl-2′,5′-bis-O-(tert-butyldimethylsilyl)-L-cyti dine ent-2A Analogous to the reaction of 1 to give 2A, 4-N-benzoyl-L-cytidine ent-1 (3.41 g, 21.9 mmol) afforded ent-2A (2.12 g, 51.2% yield). [α]D ²⁰ -41.75 (0.80, CHCl ₃ ); ¹ H and ¹³ C NMR spectroscopic data were identical to those for the enantiomer. HRMS (ESI/QTOF) m/z: [M + Na] ⁺ : Calculated for C ₂₈ H ₄₅ N ₃ O ₆ Si ₂ Na ⁺ , 598.2739; Found 598.2748. Example 18: 1-(2′,5′-Bis-O-(tert-butyldimethylsilyl)-3′-iodo-β-L- threo- pentofuranosyl)-4-N-benzoylcytosine ent-3A Analogous to the reaction of 2A to give 3A, compound ent-2A (2.04 g, 3.55 mmol) afforded ent-3A. [α]D ²⁰ -35.14 (0.35, CHCl ₃ ); ¹ H and ¹³ C NMR spectroscopic data were identical to those for the enantiomer. HRMS (ESI/QTOF) m/z: [M + Na] ⁺ : Calculated for C ₂₈ H ₄₄ IN ₃ O ₅ Si ₂ Na ⁺ , 708.1756; Found 708.1760. Example 19: 1-(2′-O-(tert-Butyldimethylsilyl)-3′-iodo-β-L-threo-pen tofuranosyl)- 4-N-benzoylcytosine (ent-4A) Analogous to the reaction of 3A to give 4A, compound ent-3A afforded ent-4A (1.12 g, 55% over two steps). [α]D ²⁰ -32.86 (1.05, CHCl ₃ ); ¹ H and ¹³ C NMR spectroscopic data were identical to those for the enantiomer. HRMS (ESI/QTOF) m/z: [M - H]-: Calculated for C ₂₂ H29IN ₃ O ₅ Si-, 570.0927; Found 570.0917. Example 20: 4-N-Benzoyl-2′-O-(tert-butyldimethylsilyl)-3’-deoxy-3’ ,4’-didehydro- L-cytidine (ent-5A) Analogous to the reaction of 4A to give 5A, compound ent-4A (1.01 g, 1.77 mmol) afforded ent-5A (302 mg, 39% yield). [α]D ²⁰ +52.48 (1.05, CHCl ₃ ); ¹ H and ¹³ C NMR spectroscopic data were identical to those for the enantiomer. HRMS (ESI/QTOF) m/z: [M - H]-: Calculated for C ₂₂ H ₂₈ N ₃ O ₅ Si-, 442.1804; Found 442.1796. Example 21: Di-tert-butyl-4-N-benzoyl-2′-O-(tert-butyldimethylsilyl)-3 ′-deoxy- 3′,4′-didehydrocytidine-5′-phosphate (9) To a solution of 4-N-benzoyl-2′-O-(tert-butyldimethylsilyl)-3′-deoxy-3′ ,4′- didehydrocytidine (5A) (1.41 g, 3.18 mmol) in anhydrous MeCN (16 mL) at room temperature was added 1H-tetrazole (0.45 M in MeCN, 21.0 mL, 9.45 mmol), followed by di-tert-butyl N,N-diisopropylphosphoramidite (1.60 mL, 5.07 mmol) dropwise. The reaction mixture was stirred for 1 h, then cooled to 0 ℃, and tert-butyl hydroperoxide (70 w/w% in H ₂ O, 1.10 mL, 7.95 mmol) was added dropwise. The reaction mixture was allowed to warm to room temperature slowly over 2 h, then quenched by addition of sat aq NaHCO ₃ (25 mL). The reaction mixture was diluted with water (50 mL) and the aqueous layer extracted with EtOAc (3 × 50 mL). The combined organic layers were washed with brine (30 mL), dried over anhydrous MgSO ₄ , filtered and concentrated in vacuo. The crude oil was purified by FCC (80 g silica gel, 20%–100% EtOAc-pet ether) to afford the title compound (1.62 g, 80%) as a colourless foam. ¹ H NMR (500 MHz, CDCl ₃ ) δ 7.91 (d, J = 7.5 Hz, 2H), 7.67 (d, J = 7.5 Hz, 1H), 7.62–7.59 (m, 1H), 7.57–7.41 (m, 3H), 6.36 (d, J = 1.5 Hz, 1H), 5.30 (d, J = 2.5 Hz, 1H), 4.88–4.79 (m, 1H), 4.70–4.56 (m, 2H), 1.50 (s, 18H), 0.89 (s, 9H), 0.17 (s, 3H), 0.10 (s, 3H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 162.6, 157.1 (d, J = 8.7 Hz), 154.4, 143.6, 133.4, 133.2, 129.2, 127.8, 104.0, 97.0, 94.5, 83.34 (d, J = 7.3 Hz), 83.29 (d, J = 7.0 Hz), 80.7, 60.7 (d, J = 4.8 Hz), 30.0 (d, J = 4.2 Hz), 25.9, 18.2, −4.4, −4.8; ³¹ P NMR (202 MHz, CDCl ₃ ) δ −9.9; HRMS (ESI+): Calculated for C30H ₄ 6N ₃ O8NaSiP: 658.2689. Found [M + Na] ⁺ : 658.2697. Example 22: Di-tert-butyl-2′-O-(tert-butyldimethylsilyl)-3′-deoxy-3� ��,4′- didehydrocytidine-5′-phosphate (10) Di-tert-butyl-4-N-benzoyl-2′-O-(tert-butyldimethylsilyl)-3 ′-deoxy-3′,4′- didehydrocytidine-5′-phosphate (9) (220 mg, 0.346 mmol) was dissolved in a solution of ammonia (7 M in MeOH, 3.5 mL, 25.0 mmol) and the resulting solution was stirred at room temperature for 18 h, then concentrated in vacuo. The crude oil was purified by flash chromatography (25 g silica gel, 1%–20% MeOH-CH ₂ Cl ₂ ) to afford the title compound (147 mg, 80%) as a colourless foam. ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.17 (s, 1H), 7.05 (d, J = 7.5 Hz, 1H), 6.93 (s, 1H), 6.24 (d, J = 2.3 Hz, 1H), 5.99 (d, J = 7.5 Hz, 1H), 5.22–5.16 (m, 1H), 4.89 (br s, 1H), 4.54–4.45 (m, 2H), 1.44 (d, J = 2.1 Hz, 18H), 0.83 (s, 9H), 0.05 (s, 3H), 0.02 (s, 3H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 166.3, 157.2 (d, J = 8.9 Hz), 155.5, 140.0, 102.8, 96.3, 95.0, 83.2 (d, J = 7.9 Hz), 83.1 (d, J = 7.8 Hz), 80.3, 60. 9 (d, J = 4.9 Hz), 29.9 (d, J = 2.9 Hz), 25.8, 18.1, −4.5, −4.7; ³¹ P NMR (202 MHz, CDCl ₃ ) δ −10.1; HRMS (ESI+): Calculated for C23H ₄ 2N ₃ O ₇ NaPSi: 554.2427. Found [M + Na] ⁺ : 554.2437. Example 23: 2′-O-(tert-Butyldimethylsilyl)-3′-deoxy-3′,4′-didehy drocytidine-5′- phosphate triethylammonium salt (11) To a solution of di-tert-butyl-2′-O-(tert-butyldimethylsilyl)-3′-deoxy-3� ��,4′- didehydrocytidine-5′-phosphate (10) (177 mg, 0.333 mmol) in MeCN (3.3 mL) under argon at room temperature was added Et ₃ N (1.9 mL, 14 mmol) followed by TMSCl (1.3 mL, 10 mmol). The reaction mixture was then placed in a pre-heated heating block at 75 ℃ and stirred at this temperature for 2 h. The reaction mixture was allowed to cool to 40 ℃, then volatiles were removed from the reaction mixture in vacuo, while still under an inert atmosphere. The slurry thus obtained was co-evaporated twice with MeCN to remove any residual volatile impurities, then purified by flash chromatography (12 g C18 column, 10%– 100% MeOH/H ₂ O with 0.5% Et ₃ N) to afford the title compound (131 mg, 76%) as a colourless solid. ¹ H NMR (500 MHz, Methanol-d4) δ 7.51 (d, J = 7.6 Hz, 1H), 6.29 (d, J = 1.7 Hz, 1H), 5.95 (d, J = 7.5 Hz, 1H), 5.34 (d, J = 2.4 Hz, 1H), 4.90 (s, 1H), 4.55–4.46 (m, 2H), 3.19 (q, J = 7.3 Hz, 6H), 1.31 (t, J = 7.3 Hz, 9H), 0.90 (s, 9H), 0.13 (s, 3H), 0.10 (s, 3H); ¹³ C NMR (126 MHz, Methanol-d4) δ 166.9, 160.7 (d, J = 8.9 Hz), 156.8, 142.3, 103.2, 96.6, 95.1, 82.0, 60.6 (d, J = 3.8 Hz), 47.7, 26.2, 18.9, 9.2, −4.50, –4.55; ³¹ P NMR (202 MHz, Methanol-d4) δ 0.92; HRMS (ESI−): Calculated for C ₁₅ H ₂₅ N ₃ O ₇ PSi: 418.1199. Found [M − H] ⁻ : 418.1198. Example 24: Difluorenylmethyl-4-N-benzoyl-2′-O-(tert-butyldimethylsily l)-3′- deoxy-3′,4′-didehydrocytidine-5′-phosphate (12) To a solution of 4-N-benzoyl-2′-O-(tert-butyldimethylsilyl)-3′-deoxy-3′ ,4′- didehydrocytidine (5A) (1.39 g, 3.13 mmol) in anhydrous MeCN (21 mL) at room temperature was added 1H-tetrazole (0.45 M in MeCN, 18.0 mL, 8.10 mmol), followed by difluorenyl N,N-diisopropylphosphoramidite (1.0 M in benzene, 4.95 mL, 4.95 mmol) dropwise. The reaction mixture was stirred for 1 h, then cooled to 0 ℃, and tert-butyl hydroperoxide (70 w/w% in H ₂ O, 1.10 mL, 7.95 mmol) was added dropwise. The reaction mixture was allowed to warm to room temperature and stirred for 90 min, then quenched by addition of 10% aq Na ₂ S ₂ O ₃ (5 mL) and sat aq NaHCO ₃ (100 mL). The reaction mixture was extracted with EtOAc (3 × 50 mL) and the combined organic layers were washed with brine (30 mL), dried over anhydrous MgSO ₄ , filtered and concentrated in vacuo. The crude oil was purified by flash column chromatography (120 g silica gel, 5%–50% EtOAc-PhMe) to afford the title compound (2.39 g, 87%) as a pale-yellow foam. ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.88 (s, 1H), 7.92 (d, J = 7.6 Hz, 2H), 7.75–7.68 (m, 4H), 7.59 (t, J = 7.4 Hz, 1H), 7.54 (d, J = 7.5 Hz, 2H), 7.52–7.46 (m, 4H), 7.44–7.23 (m, 10H), 6.30 (d, J = 2.0 Hz, 1H), 5.12 (d, J = 2.7 Hz, 1H), 4.80 (t, J = 2.2 Hz, 1H), 4.50–4.38 (m, 2H), 4.37–4.28 (m, 4H), 4.13 (td, J = 6.4, 2.9 Hz, 2H), 0.89 (s, 9H), 0.15 (s, 3H), 0.09 (s, 3H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 166.7, 162.4, 156.0 (d, J = 6.9 Hz), 155.9, 154.1, 143.1, 142.9, 141.4, 133.2, 129.0, 128.0, 127.7, 127.2, 125.03, 124.99, 120.10, 120.06, 104.3, 97.2, 94.5, 80.5, 69.46 (d, J = 5.2 Hz), 69.39 (d, J = 5.2 Hz), 61.2 (d, J = 5.8 Hz), 47.9 (d, J = 7.5 Hz), 25.8, 18.1, −4.5, −4.8; ³¹ P NMR (202 MHz, CDCl ₃ ) δ −1.6; HRMS (ESI+): Calculated for C ₅₀ H ₅₁ N ₃ O ₈ SiP: 880.3183. Found [M + H] ⁺ : 880.3185. Example 25: 2′-O-(tert-Butyldimethylsilyl)-3′-deoxy-3′,4′-didehy drocytidine-5′- phosphate triethylammonium salt (11) Difluorenylmethyl-4-N-benzoyl-2′-O-(tert-butyldimethylsily l)-3′-deoxy-3′,4′- didehydrocytidine-5′-phosphate (12) (2.20 g, 2.50 mmol) was dissolved in a 7 M solution of anhydrous NH3 in MeOH (25 mL) and stirred at room temperature for 18 h. The crude reaction mixture was then adsorbed onto Celite ^® for purification by dry load – Celite ^® (approximately 6 g) was added to the reaction mixture and the resulting suspension was concentrated in vacuo until a dry, free-flowing solid mixture was obtained. Purification by flash column chromatography (40 g silica gel, 10–100% MeOH/NH ₄ OH-EtOAc) afforded the product as an ammonium salt, which was then co-evaporated three times with MeOH and Et ₃ N to afford the title compound (1.03 g, 79% yield) as a colourless solid. ¹ H NMR (500 MHz, Methanol-d4) δ 7.51 (d, J = 7.6 Hz, 1H), 6.29 (d, J = 1.7 Hz, 1H), 5.95 (d, J = 7.5 Hz, 1H), 5.34 (d, J = 2.4 Hz, 1H), 4.90 (s, 1H), 4.55–4.46 (m, 2H), 3.19 (q, J = 7.3 Hz, 6H), 1.31 (t, J = 7.3 Hz, 9H), 0.90 (s, 9H), 0.13 (s, 3H), 0.10 (s, 3H); ¹³ C NMR (126 MHz, Methanol-d4) δ 166.9, 160.7 (d, J = 8.9 Hz), 156.8, 142.3, 103.2, 96.6, 95.1, 82.0, 60.6 (d, J = 3.8 Hz), 47.7, 26.2, 18.9, 9.2, −4.50, –4.55; ³¹ P NMR (202 MHz, Methanol-d4) δ 0.92; HRMS (ESI−): Calculated for C ₁₅ H ₂₅ N ₃ O ₇ PSi: 418.1199. Found [M − H] ⁻ : 418.1198. Example 26: 2′-O-(tert-Butyldimethylsilyl)-3′-deoxy-3′,4′-didehy drocytidine (13) 4-N-Benzoyl-2′-O-tert-butyldimethylsilyl-3′-deoxy-3′,4 ′-didehydrocytidine (5A) (500 mg, 1.13 mmol) was dissolved in a solution of NH3 (7 M in MeOH, 11.3 mL, 79.1 mmol) and the resulting mixture was stirred at r.t. for 3 h. The reaction mixture was concentrated in vacuo and the crude oil triturated with a small quantity of EtOAc. The precipitate was collected by vacuum filtration, washing with a small quantity of Et2O to afford the title compound (297 mg, 78%) as a colourless solid. ¹ H NMR (500 MHz, DMSO- d6) δ 7.27 (br s, 1H), 7.25 (d, J = 7.4 Hz, 1H), 7.19 (br s, 1H), 6.18 (d, J = 2.2 Hz, 1H), 5.73 (d, J = 7.4 Hz, 1H), 5.28 (t, J = 5.8 Hz, 1H), 5.12–5.09 (m, 1H), 4.88–4.85 (m, 1H), 4.04 (d, J = 4.9 Hz, 2H), 0.84 (s, 9H), 0.06 (s, 3H), 0.04 (s, 3H); ¹³ C NMR (126 MHz, DMSO-d6) δ 165.6, 162.3, 154.6, 140.3, 99.6, 94.9, 93.2, 79.9, 56.1, 25.7, 17.7, −4.7, −4.8; HRMS (ESI+): Calculated for C ₁₅ H25N ₃ O ₄ NaSi: 362.1512. Found [M + Na] ⁺ : 362.1507. ^{Example 27: Difluorenylmethyl-2′-O-(tert-butyldimethylsilyl)-3′-deox y-3′,4′-} didehydrocytidine-5′-phosphate (14) To a suspension of 2′-O-(tert-butyldimethylsilyl)-3′-deoxy-3′,4′-didehy drocytidine (13) (100 mg, 0.295 mmol) in MeCN (1.5 mL) at room temperature was added a solution of 1H-tetrazole (0.45 M in MeCN, 1.6 mL, 0.72 mmol), followed by a solution of difluorenyl N,N-diisopropylphosphoramidite (1.0 M in benzene, 0.37 mL, 0.37 mmol) dropwise. The reaction mixture was stirred for 1 h, then cooled to 0 ℃, and tert-butyl hydroperoxide (70 w/w% in H ₂ O, 85 µL, 0.61 mmol) was added dropwise. The reaction mixture was allowed to warm to room temperature and stirred for 90 min, then quenched by addition of 10% aq Na ₂ S ₂ O ₃ (1 mL) and sat aq NaHCO ₃ (10 mL). The reaction mixture was extracted with EtOAc (3 × 10 mL) and the combined organic layers were washed with brine (5 mL), dried over anhydrous MgSO ₄ , filtered and concentrated in vacuo. The crude oil was purified by flash column chromatography (12 g silica gel, 60%–100% EtOAc-Hex) to afford the title compound (170 mg, 74%) as an off-white foam. ¹ H NMR (500 MHz, CDCl ₃ ) δ 7.75–7.64 (m, 4H), 7.55–7.49 (m, 4H), 7.49–7.41 (m, 2H), 7.40–7.30 (m, 4H), 7.30–7.19 (m, 4H), 6.95 (d, J = 7.5 Hz, 1H), 6.25 (d, J = 2.3 Hz, 1H), 5.44 (d, J = 7.5 Hz, 1H), 5.08 (d, J = 2.6 Hz, 1H), 4.80 (t, J = 2.4 Hz, 1H), 4.46–4.34 (m, 2H), 4.34–4.21 (m, 4H), 4.16–4.08 (m, 3H), 0.86 (s, 10H), 0.08 (s, 3H), 0.04 (s, 3H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 165.8, 156.2 (d, J = 7.2 Hz), 155.2, 143.0, 141.51, 141.47, 140.2, 128.1, 127.32, 127.28, 125.2, 125.1, 120.1, 104.0, 95.4, 94.7, 80.4, 69.5 (d, J = 6.2 Hz), 61.5 (d, J = 5.2 Hz), 48.0 (d, J = 11.0 Hz), 25.9, 18.2, −4.4, −4.7; ³¹ P NMR (202 MHz, CDCl ₃ ) δ −1.8; HRMS (ESI+): Calculated for C ₄₃ H ₄₆ N ₃ O ₇ NaSiP: 798.2740. Found [M + Na] ⁺ : 798.2739. Example 28: 2′-O-(tert-Butyldimethylsilyl)-3′-deoxy-3′,4′-didehy drocytidine-5′- phosphate triethylammonium salt (11) Difluorenylmethyl-2′-O-(tert-butyldimethylsilyl)-3′-deox y-3′,4′-didehydrocytidine-5′- phosphate (14) (100 mg, 0.295 mmol) was dissolved in a solution of MeCN-Et ₃ N (1:1, 1.3 mL) and stirred at room temperature for 18 h. The crude reaction mixture was then adsorbed onto Celite ^® for purification by dry load – Celite ^® (approximately 1 g) was added to the reaction mixture and the resulting suspension was concentrated in vacuo until a dry, free-flowing solid mixture was obtained. Purification by flash column chromatography (4 g silica gel, 10–100% MeOH/NH ₄ OH-EtOAc) afforded the product as an ammonium salt, which was then co-evaporated three times with MeOH and Et ₃ N to afford the title compound (67.1 mg, 94% yield) as a colourless solid. Example 29: 2′-O-tert-Butyldimethylsilyl-3′,4′-didehydro-3′-deox y-4-N- (4,4′-dimethoxytrityl)-cytidine (15) To a solution of 2′-O-tert-butyldimethylsilyl-3′,4′-didehydro-3′-deox ycytidine (13) (100 mg, 0.295 mmol) in pyridine (1.5 mL) at room temperature was added chlorotrimethylsilane (80 µL, 0.6 mmol). The reaction mixture was stirred for 45 min, then 4,4′-dimethoxytrityl chloride (126 mg, 0.361 mmol) was added and the mixture left stirring overnight. The reaction was then quenched by addition of NH ₄ OH (28% w/w in water, 60 µL, 0.4 mmol) and water (1 mL), stirred for 15 min, and diluted with EtOAc (50 mL). The organic layer was washed with 1 M aq HCl (2 × 20 mL), water (20 mL) and brine (15 mL), dried over anhydrous MgSO ₄ , filtered and concentrated in vacuo. Purification by flash column chromatography on silica gel (50–100% EtOAc-Hex, then 0–10% MeOH-EtOAc) afforded the title compound (126 mg, 67% yield) as a pale yellow solid. ¹ H NMR (500 MHz, CDCl ₃ ) δ 7.33–7.24 (m, 3H), 7.23–7.19 (m, 2H), 7.15–7.09 (m, 4H), 6.87 (d, J = 7.7 Hz, 1H), 6.85–6.79 (m, 4H), 6.23 (d, J = 1.9 Hz, 1H), 5.10 (dd, J = 2.5, 1.2 Hz, 1H), 5.02 (d, J = 7.6 Hz, 1H), 4.85 (d, J = 2.2 Hz, 1H), 4.23 (s, 2H), 3.80 (s, 6H), 0.88 (s, 9H), 0.13 (s, 3H), 0.08 (s, 3H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 165.7, 160.6, 158.9, 154.8, 144.7, 140.1, 136.4, 130.0, 128.6, 128.5, 127.6, 113.8, 101.3, 95.1, 95.0, 80.5, 70.3, 58.1, 55.4, 25.9, 18.3, −4.3, −4.6; HRMS (ESI/Q-TOF) m/z [M + Na] ⁺ Calcd for C ₃₆ H ₄₃ N ₃ O ₆ NaSi: 664.2819; Found 664.2827. Example 30: 3′-Deoxy-3′,4′-didehydrocytidine-5′-phosphate sodium salt (16) 2′-O-(tert-Butyldimethylsilyl)-3′-deoxy-3′,4′-didehy drocytidine-5′-phosphate triethylammonium salt (11) (115 mg, 0.221 mmol) was dissolved in AcOH-DI H ₂ O (1:1, 4.4 mL) and the resulting solution was stirred at room temperature for 18 h, then concentrated in vacuo at or below 40 ℃. The residue obtained was co-evaporated with DI H ₂ O three times to remove residual AcOH, affording the triethylammonium phosphate as a colourless solid. This solid was dissolved in DI H ₂ O and passed through an ion-exchange column (1 g Dowex® 50W X8 Na-form), eluting with DI H ₂ O. The product-containing fractions were combined and passed through a Sep-Pak C18 cartridge, then lyophilized to afford the title compound (74 mg, quant) as a colourless solid. ¹ H NMR (500 MHz, D ₂ O) δ 7.50 (d, J = 7.5 Hz, 1H), 6.33 (d, J = 2.1 Hz, 1H), 6.07 (d, J = 7.6 Hz), 5.52 (d, J = 2.6 Hz, 1H), 4.98–4.94 (m, 1H), 4.64–4.55 (m, 2H); ¹³ C NMR (126 MHz, D ₂ O) δ 165.9, 158.8 (d, J = 7.6 Hz), 156.6, 141.2, 101.8, 96.4, 93.7, 78.7, 59.4 (d, J = 4.1 Hz); ³¹ P NMR (202 MHz, D ₂ O) δ 0.69; HRMS (ESI−): Calculated for C9H11N ₃ O ₇ P: 304.0335. Found [M − H] ⁻ : 304.0343. Example 31: 2′-O-(tert-Butyldimethylsilyl)-3′-deoxy-3′,4′-didehy drocytidine-5′- diphosphate bis(triethylammonium) salt (17) 2′-O-(tert-Butyldimethylsilyl)-3′-deoxy-3′,4′-didehy drocytidine-5′-phosphate triethylammonium salt (11) (100 mg, 0.192 mmol) and CDI (160 mg, 0.937 mmol) were dissolved in MeCN (1.9 mL) under argon and stirred at room temperature for 20 h, then excess CDI was quenched by addition of H ₂ O (30 µL, 1.7 mmol). The reaction mixture was stirred for 1 h, then loaded onto Dowex ^® 50WX8 Et ₃ NH form and eluted with MeCN to remove imidazole from the crude mixture. Fractions containing the intermediate imidazolidate were combined and concentrated in vacuo to dryness. The crude imidazolidate was dissolved in MeCN (1.0 mL), to which solution was added tributylammonium phosphate (1 M in MeCN, 0.96 mL, 0.96 mmol). The reaction mixture was stirred at room temperature for 24 h, then concentrated in vacuo. The crude residue dissolved in DI H ₂ O and passed through an ion exchange column (Dowex ^® 50WX8 Et ₃ NH form) eluting with DI H ₂ O to convert the diphosphate product to its di(triethylammonium) salt form. Product-containing fractions were combined, then concentrated in vacuo. The crude oil thus obtained was purified by flash chromatography (24 g C18 column, 5%–100% MeOH-H ₂ O) to afford the title compound (82 mg, 61% yield) as a colourless solid. ¹ H NMR (500 MHz, Methanol-d4) δ 7.61 (d, J = 7.7 Hz, 1H), 6.22 (d, J = 1.7 Hz, 1H), 6.11 (d, J = 7.7 Hz, 1H), 5.40 (d, J = 2.7 Hz, 1H), 4.94–4.91 (m, 1H), 4.74–4.64 (m, 2H), 3.19 (q, J = 7.3 Hz, 8H), 1.31 (t, J = 7.3 Hz, 12H), 0.90 (s, 9H), 0.13 (s, 3H), 0.10 (s, 3H); ¹³ C NMR (126 MHz, Methanol-d4) δ 163.8, 160.2 (d, J = 9.1 Hz), 152.5, 143.4, 103.9, 96.6, 94.9, 81.7, 61.2 (d, J = 4.2 Hz), 47.4, 26.2, 18.9, 9.1, −4.5; ³¹ P NMR (202 MHz, Methanol-d4) δ −10.02 (d, J = 19.3 Hz), −11.11 (d, J = 19.3 Hz); HRMS (ESI−): Calculated for C ₁₅ H ₂₆ N ₃ O ₁₀ P ₂ Si: 498.0863. Found [M − H] ⁻ : 498.0872. Example 32: 3′-Deoxy-3′,4′-didehydrocytidine-5′-diphosphate bis(triethylammonium) salt (18) To a solution of 2′-O-(tert-butyldimethylsilyl)-3′-deoxy-3′,4′-didehy drocytidine-5′- diphosphate di(triethylammonium) salt (17) (75 mg, 0.107 mmol) in deionized water (10 mL) was added Dowex® 50WX8 hydrogen form (218 mg), which had previously been washed with MeOH and deionized water. The suspension was stirred at room temperature for 1 h then the reaction mixture was neutralised by addition of Et ₃ N (0.3 mL) and stirred for a further 5 min. The reaction mixture was filtered and the resin was washed with deionized water (3 × 5 mL). The filtrate and combined washings were concentrated in vacuo at 40 ℃ to approximately 5 mL in volume, then lyophilized to afford the title compound (65 mg, quant) as a colourless solid. ¹ H NMR (500 MHz, D ₂ O) δ 7.52 (d, J = 7.6 Hz, 1H), 6.35 (br s, 1H), 6.08 (d, J = 7.6 Hz, 1H), 5.54 (br s, 1H), 4.93 (br s, 1H), 4.75–4.62 (m, 2H), 3.24 (q, J = 7.3 Hz, 12H), 1.32 (t, J = 6.6 Hz, 18H); ¹³ C NMR (126 MHz, D ₂ O) δ 166.2, 158.6 (d, J = 8.1 Hz), 157.0, 141.1, 101.8, 96.5, 93.5, 78.8, 60.0 (d, J = 4.8 Hz), 46.7, 8.1; ³¹ P NMR (202 MHz, D ₂ O) δ −9.47 (d, J = 21.8 Hz), −11.23 (d, J = 21.1 Hz).; HRMS (ESI−): Calculated for C9H12N ₃ O10P2: 383.9998. Found [M − H] ⁻ : 384.0007. Example 33: 2′-O-(tert-Butyldimethylsilyl)-3′-deoxy-3′,4′-didehy drocytidine-5′- triphosphate tris(triethylammonium) salt (19) 2′-O-(tert-Butyldimethylsilyl)-3′-deoxy-3′,4′-didehy drocytidine-5′-phosphate triethylammonium salt (11) (100 mg, 0.192 mmol) and CDI (171 mg, 1.01 mmol) were dissolved in MeCN (2.0 mL) under argon and stirred at room temperature for 20 h, then excess CDI was quenched by addition of H ₂ O (28 µL, 1.6 mmol). The reaction mixture was stirred for 1 h, then bis(tributylammonium) pyrophosphate (530 mg, 0.966 mmol) was added and the reaction mixture stirred for a further 48 h, after which the reaction was complete by TLC analysis (silica gel, 6:1:3 i-PrOH-H ₂ O-28% aq NH ₄ OH). The reaction solvent was removed in vacuo, then the crude triphosphate was dissolved in DI H ₂ O and converted to its triethylammonium salt by passage through an ion exchange column (Dowex ^® 50WX8 Et ₃ NH form) eluting with DI H ₂ O. Product-containing fractions were combined, then concentrated in vacuo. The crude oil thus obtained was purified by flash chromatography (24 g C18 column, 10%–100% MeOH-H ₂ O) to afford the title compound (149 mg, 88%) as a colourless solid after lyophilization. ¹ H NMR (500 MHz, D ₂ O) δ 7.55 (d, J = 7.6 Hz, 1H), 6.42 (d, J = 1.9 Hz, 1H), 6.13 (d, J = 7.5 Hz, 1H), 5.59 (d, J = 1.6 Hz, 1H), 5.19 (br s, 1), 4.75–4.64 (m, 2H), 3.26 (q, J = 7.3 Hz, 18H), 1.34 (t, J = 7.3 Hz), 0.95 (s, 9H), 0.21 (s, 3H), 0.18 (s, 3H); ¹³ C NMR (126 MHz, D ₂ O) δ 166.2, 158.2 (d, J = 8.2 Hz), 156.9, 141.4, 102.6, 96.9, 93.6, 80.8, 60.4 (d, J = 4.5 Hz), 46.7, 25.1, 17.5, 8.39, −5.58, −5.65; ³¹ P NMR (202 MHz, D ₂ O) δ −10.64 (d, J = 19.8 Hz), −11.43 (d, J = 19.9 Hz), −23.25 (t, J = 19.9 Hz); HRMS (ESI−): Calculated for C ₁₅ H ₂₇ N ₃ O ₁₃ P ₃ Si: 578.0526. Found [M − H] ⁻ : 578.0535. Example 34: 3′-Deoxy-3′,4′-didehydrocytidine-5′-triphosphate tris(triethylammonium) salt (20) To a solution of 2′-O-(tert-butyldimethylsilyl)-3′-deoxy-3′,4′-didehy drocytidine-5′- triphosphate tris(triethylammonium) salt (19) (97 mg, 0.110 mmol) in deionized water (10 mL) was added Dowex® 50WX8 hydrogen form (216 mg), which had previously been washed with MeOH and deionized water. The suspension was stirred at room temperature for 1 h then the reaction mixture was neutralised by addition of Et ₃ N (0.3 mL) and stirred for a further 5 min. The reaction mixture was filtered and the resin was washed with deionized water (3 × 5 mL). The filtrate and combined washings were concentrated in vacuo at 40 ℃ to approximately 5 mL in volume, then lyophilized to afford the title compound (80 mg, 95% yield) as a colourless solid. ¹ H NMR (500 MHz, D ₂ O) δ 7.52 (d, J = 7.6 Hz, 1H), 6.36 (br s, 1H), 6.09 (d, J = 7.6 Hz, 1H), 5.56 (br s, 1H), 4.93 (br s, 1H), 4.75–4.67 (m, 2H), 3.23 (q, J = 7.3 Hz, 21H), 1.31 (t, J = 7.3 Hz, 31H); ¹³ C NMR (126 MHz, D ₂ O) δ 166.2, 158.4 (d, J = 8.1 Hz), 157.0, 141.1, 102.0, 96.5, 93.5, 78.8, 60.3 (d, J = 5.2 Hz),.46.7, 8.1; ³¹ P NMR (202 MHz, D ₂ O) δ −10.20 (d, J = 20.5 Hz), −11.49 (d, J = 19.9 Hz), −23.26 (t, J = 20.2 Hz); HRMS (ESI−): Calculated for C ₉ H ₁₃ N ₃ O ₁₃ P ₃ : 463.9661. Found [M − H] ⁻ : 463.9669. Example 35: 2′,5′-Bis-O-(tert-butyldimethylsilyl)uridine (22) The title compound was prepared according to a literature procedure (Can. J. Chem. 1978, 56(2), 2768–2780). To a solution of uridine (21) (20.0 g, 8.19 mmol) in anhydrous pyridine (16.4 mL) at room temperature was added tert-butyldimethylsilyl chloride (3.82 g, 24.6 mmol). The reaction mixture was stirred for 3 d, then concentrated in vacuo. The resultant oil was dissolved in CHCl ₃ (50 mL) and washed with 0.5 M aq HCl (100 mL). The aqueous layer was back-extracted with CHCl ₃ (2 × 50 mL), then the combined organic layers were washed with brine (40 mL), dried over anhydrous MgSO ₄ , filtered and concentrated in vacuo. Purification by flash column chromatography (silica gel, 5%–60% EtOAc-Hex) afforded the title compound (2.47 g, 63% yield) as a colourless foam. ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.42 (s, 1H), 7.98 (d, J = 8.2 Hz, 1H), 5.97 (d, J = 4.3 Hz, 1H), 5.69 (dd, J = 8.1, 2.3 Hz, 1H), 4.20 (t, J = 4.4 Hz, 1H), 4.16–4.07 (m, 2H), 3.99 (dd, J = 11.6, 1.8 Hz, 1H), 3.82 (dd, J = 11.6, 1.7 Hz, 1H), 2.60 (d, J = 5.0 Hz, 1H), 0.94 (s, 9H), 0.91 (s, 9H), 0.14–0.11 (m, 9H), 0.09 (s, 3H). Example 36: 1-(2′,5′-Bis-O-(tert-butyldimethylsilyl)-3′-iodo-β-D- threo- pentofuranosyl)-uracil (23) To a solution of triphenylphosphine (113 mg, 0.422 mmol), imidazole (58 mg, 0.843 mmol) and I2 (108 mg, 0.426 mmol) in THF (3.0 mL) at room temperature was added a solution of 2′,5′-bis-O-(tert-butyldimethylsilyl)uridine (22) (100 mg, 0.212 mmol) in THF (2.1 mL). The reaction mixture was heated to 60 °C and stirred for 4 h, then cooled to room temperature. The reaction mixture was diluted with EtOAc (15 mL), then silica gel (750 mg) was added to form a slurry. The slurry was concentrated in vacuo to give a free- flowing solid mixture was purification by dry load; flash column chromatography (25 g silica gel, 5–50% EtOAc-Hex) afforded the title compound (99.8 mg, 81% yield) as a colourless solid. ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.98 (s, 1H), 7.86 (d, J = 8.2 Hz, 1H), 5.77 (d, J = 3.6 Hz, 1H), 5.74 (d, J = 8.2 Hz, 1H), 4.61 (t, J = 4.2 Hz, 1H), 4.23 (t, J = 5.1 Hz, 1H), 4.06–3.98 (m, 2H), 3.89–3.83 (m, 1H), 0.94 (s, 9H), 0.89 (s, 9H), 0.16 (s, 3H), 0.14 (s, 3H), 0.14 (s, 3H), 0.07 (s, 3H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 163.3, 150.4, 140.5, 102.1, 90.5, 82.6, 80.5, 67.6, 28.7, 26.1, 25.7, 18.5, 17.9, −4.3, −4.7, −5.0, −5.3; HRMS (ESI+): Calculated for C ₂₁ H ₄₀ N ₂ O ₅ Si ₂ I: 583.1520. Found [M + H] ⁺ : 583.1517. Example 37: 1-(2′-O-(tert-Butyldimethylsilyl)-3′-iodo-β-D-threo-pen tofuranosyl)- uracil (24) To a solution of 1-(2′,5′-bis-O-(tert-butyldimethylsilyl)-3′-iodo-β-D- threo- pentofuranosyl)-uracil (23) (131 mg, 0.225 mmol) in THF (0.5 mL) at 0 ℃ was added a mixture of TFA-H ₂ O (1:1, 0.14 mL) dropwise over 3 min. The reaction mixture was warmed to room temperature and stirred for 3.5 h. The reaction was neutralised by addition of sat aq NaHCO ₃ (5 mL), then extracted with EtOAc (3 × 5 mL). The combined organic layers were washed with sat aq NaHCO ₃ (5 mL), brine (5 mL), dried over anhydrous MgSO ₄ , filtered and concentrated in vacuo. The crude oil was purified by flash column chromatography (12 g silica gel, 15%–80% EtOAc-Hex) to afford the title compound (90 mg, 85% yield) as a colourless solid. ¹ H NMR (500 MHz, CDCl ₃ ) δ 7.78 (d, J = 8.2 Hz, 1H), 5.77 (d, J = 8.0 Hz, 1H), 5.69 (d, J = 3.0 Hz, 1H), 4.71 (t, J = 3.5 Hz, 1H), 4.19 (dd, J = 5.4, 3.6 Hz, 1H), 4.08 (td, J = 5.4, 3.6 Hz, 1H), 4.01 (dd, J = 11.8, 5.2 Hz, 1H), 3.85 (dd, J = 11.9, 3.9 Hz, 1H), 0.88 (s, 9H), 0.14 (s, 3H), 0.09 (s, 3H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 163.7, 150.4, 140.9, 102.1, 92.0, 83.4, 80.7, 67.5, 28.5, 25.2, 17.9, −4.4, −4.7; HRMS (ESI+): Calculated for C ₁₅ H25N ₂ O ₅ NaSiI: 491.0475. Found [M + Na] ⁺ : 491.0475. Example 38: 2′-O-(tert-Butyldimethylsilyl)-3′-deoxy-3′,4′-didehy drouridine (25) 1-(2′-O-(tert-Butyldimethylsilyl)-3′-iodo-β-D-threo-pen tofuranosyl)-uracil (24) (88 mg, 0.188 mmol) and DABCO (75 mg, 0.658 mmol) were dissolved in PhMe (3.8 mL), then heated to 75 °C and stirred for 18 h. The reaction mixture was cooled to room temperature, then filtered through a pad of Celite ^® , washing with EtOAc. The filtrate was concentrated in vacuo, then the crude oil obtained was purified by flash column chromatography (silica gel, 50–100% EtOAc-Hex) to afford the title compound (62 mg, 97% yield) as a colourless foam. ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.58 (s, 1H), 7.11 (d, J = 8.0 Hz, 1H), 6.28 (d, J = 2.0 Hz, 1H), 5.80–5.69 (m, 1H), 5.24–5.18 (m, 1H), 4.91 (t, J = 2.3 Hz, 1H), 4.29 (d, J = 6.3 Hz, 2H), 0.89 (s, 9H), 0.11 (s, 3H), 0.09 (s, 3H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 162.7, 161.3, 149.8, 139.4, 103.5, 101.2, 93.6, 80.5, 58.0, 25.8, 18.2, −4.5; HRMS (ESI+): Calculated for C ₁₅ H ₂₄ N ₂ O ₅ NaSi: 363.1352. Found [M + Na] ⁺ : 363.1350. Example 39: 2′,3′-Di-O-methoxymethylidene-uridine (26) The title compound was prepared according to a literature procedure (Tetrahedron Letters, 2010, 51, 6874-6876). To uridine (21) (5.00 g, 20.5 mmol) and PTSA monohydrate (150 mg, 0.789 mmol) was added trimethyl orthoformate (12.5 mL, 110 mmol) and the resulting suspension was stirred at room temperature for 21 h. The reaction mixture was then cooled to 0 ℃ and quenched by addition of sodium methoxide (25% w/w in MeOH, 0.21 mL, 0.92 mmol) and PhMe (5 mL). The reaction mixture was concentrated in vacuo and the resultant oil purified by flash column chromatography (120 g silica gel, 3%–20% MeOH-CH ₂ Cl ₂ ) to afford the title compound (3.18 g, 54% yield) as a colourless gum. The product was an approximately 1:1 mixture of diastereomers at the orthoformate stereocentre, designated as A and B. ¹ H NMR (500 MHz, DMSO-d6) δ 11.37 (s, 1H, A+B), 7.78–7.75 (m, 1H, A+B), 6.10 (s, 0.5H, A), 6.01 (s, 0.5H, B), 5.94 (d, J = 3.2 Hz, 0.5H, B), 5.80 (d, J = 2.7 Hz, 0.5H, A), 5.65–5.62 (m, 1H, A+B), 5.11–5.02 (m, 1H, A+B), 5.02–4.97 (m, 1H, A+B), 4.85 (dd, J = 6.5, 3.9 Hz, 0.5H, A), 4.78 (dd, J = 7.3, 3.9 Hz, 0.5H, B), 4.17 (q, J = 4.8 Hz, 0.5H, B), 4.06 (q, J = 4.7 Hz, 0.5H, A), 3.65–3.54 (m, 2H, A+B), 3.30 (s, 1.5H, B), 3.21 (s, 1.5H, A). Example 40: 3′-Deoxy-3′,4′-didehydro-uridine-5′-aldehyde (27) The title compound was prepared according to a procedure adapted from Petrová et al. (Tetrahedron Letters, 2010, 51, 6874-6876). 2′,3′-Di-O-methoxymethylidene-uridine (26) (3.18 g, 11.1 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (4.50 g, 22.2 mmol) were placed under argon, then suspended in DMF (22 mL). To this suspension was added DMSO (1.6 mL, 22.2 mmol), followed by a solution of pyridine (0.91 mL, 11.1 mmoL) and TFA (0.43 mL, 5.55 mmol) in DMF (6 mL). The reaction mixture was stirred at room temperature for 1 h, after which the white suspension had become a yellow homogeneous solution. Et ₃ N (6.3 mL, 45.2 mmol) was subsequently added to the reaction mixture, which was stirred for 10 min, then oxalic acid dihydrate (1.40, 11.1 mmol) was added and the reaction mixture stirred for a further 5 min. Volatiles were removed under high vacuum at room temperature, then the crude residue was subjected to flash chromatography (6 × 12 cm silica gel, 0%–20% MeOH-CHCl ₃ ) to afford the partially purified title compound (2.16 g) as a pale yellow foam which was taken directly into the next step. ¹ H NMR (500 MHz, DMSO-d6) δ 11.47 (br s, 1H), 9.52 (s, 1H), 7.50 (d, J = 8.0 Hz, 1H), 6.47 (d, J = 2.8 Hz, 1H), 6.16 (d, J = 6.6 Hz, 1H), 6.13 (d, J = 3.8 Hz, 1H), 5.64 (s, 1H), 5.21–5.16 (m, 1H); ¹³ C NMR (126 MHz, DMSO-d6) δ 183.4, 163.0, 155.6, 150.1, 141.7, 121.7, 102.7, 94.7, 76.6. Example 41: 2′-O-(tert-Butyldimethylsilyl)-3′-deoxy-3′,4′-didehy drouridine-5′- aldehyde (28) To a solution of the impure 3′-deoxy-3′,4′-didehydrouridine-5′-aldehyde (27) (2.16 g) in DMF (19 mL) at room temperature was added Et ₃ N (4.0 mL, 29 mmol), followed by TBDMSCl (3.70 g, 24 mmol). The reaction mixture was stirred at room temperature for 2 d, then quenched by addition of EtOH (5 mL) and concentrated in vacuo. The crude residue was dissolved in EtOAc (100 mL) and washed with 0.1 M aq HCl (40 mL), sat aq NaHCO ₃ (40 mL), brine (40 mL). The organic layer was dried over anhydrous MgSO ₄ , filtered and concentrated in vacuo. Purification by flash column chromatography (80 g silica gel, 60%– 100% EtOAc-Hex) afforded the title compound (1.48 g, 46% yield) as a pale brown foam. ¹ H NMR (500 MHz, CDCl ₃ ) δ 9.80 (br s, 1H), 9.51 (s, 1H), 7.05 (d, J = 8.2 Hz, 1H), 6.12 (d, J = 2.8 Hz, 1H), 6.10 (d, J = 3.3 Hz, 1H), 5.73 (d, J = 8.0 Hz, 1H), 5.26 (t, J = 3.0 Hz, 1H), 0.87 (s, 9H), 0.10 (s, 3H), 0.09 (s, 3H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 181.6, 163.2, 156.3, 149.8, 140.5, 118.8, 103.6, 96.4, 79.2, 25.6, 18.1, −4.5, −4.6; HRMS (ESI+): Calculated for C ₁₅ H22N ₂ O ₅ NaSi: 361.1196. Found [M + Na] ⁺ : 361.1205. Example 42: 2′-O-(tert-Butyldimethylsilyl)-3′-deoxy-3′,4′-didehy drouridine (25) To a solution of 2′-O-(tert-butyldimethylsilyl)-3′-deoxy-3′,4′-didehy drouridine-5′- aldehyde (28) (2.14 g, 9.55 mmol) in MeOH (45 mL) at 0 °C was added NaBH ₄ (84 mg, 2.18 mmol). The reaction mixture was stirred at 0 °C for 30 min, then quenched by addition of acetone (0.5 mL). The reaction mixture was concentrated in vacuo, then the crude reside was purified by flash column chromatography (80 g silica gel, 0%–15% MeOH-CH ₂ Cl ₂ ) to afford the title compound (1.37 g 94% yield) as a colourless foam. ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.58 (s, 1H), 7.11 (d, J = 8.0 Hz, 1H), 6.28 (d, J = 2.0 Hz, 1H), 5.80–5.69 (m, 1H), 5.24–5.18 (m, 1H), 4.91 (t, J = 2.3 Hz, 1H), 4.29 (d, J = 6.3 Hz, 2H), 0.89 (s, 9H), 0.11 (s, 3H), 0.09 (s, 3H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 162.7, 161.3, 149.8, 139.4, 103.5, 101.2, 93.6, 80.5, 58.0, 25.8, 18.2, −4.5; HRMS (ESI+): Calculated for C ₁₅ H24N ₂ O ₅ NaSi: 363.1352. Found [M + Na] ⁺ : 363.1350. Example 43: Difluorenylmethyl 2′-O-(tert-butyldimethylsilyl)-3′-deoxy-3′,4′- didehydrouridine-5′-phosphate (29) To a solution of 2′-O-(tert-butyldimethylsilyl)-3′-deoxy-3′,4′-didehy drouridine (25) (600 mg, 1.76 mmol) and bis((9H-fluoren-9-yl)methyl) diisopropylphosphoramidite (1.50 g, 2.44 mmol) in MeCN (9 mL) at room temperature was added 1H-tetrazole (0.45 M in MeCN, 11.8 mL, 5.3 mmol). The reaction mixture was stirred for 1 h, then cooled to 0 °C and treated with tBuOOH (70% in H ₂ O, 0.59 mL, 4.23 mmol). The reaction was allowed to warm to room temperature and stirred for 90 min, then diluted with sat aq NaHCO ₃ (50 mL) and EtOAc (25 mL). The aqueous phase was extracted with EtOAc (2 × 25 ml), then the combined organic layers were washed with brine (20 mL), dried over anhydrous MgSO ₄ , filtered and concentrated in vacuo. The crude product was purified by flash column chromatography (80 g silica gel, 40%–100% EtOAc-Hex) to afford the title compound (1.24 g, 90% yield) as a colourless foam. ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.52 (s, 1H), 7.77– 7.69 (m, 4H), 7.53 (dd, J = 7.5, 2.0 Hz, 2H), 7.50–7.44 (m, 2H), 7.44–7.34 (m, 4H), 7.33– 7.23 (m, 5H), 6.90 (d, J = 8.1 Hz, 1H), 6.23 (d, J = 2.3 Hz, 1H), 5.46 (dd, J = 8.1, 2.3 Hz, 1H), 5.09 (d, J = 2.4 Hz, 1H), 4.79 (t, J = 2.4 Hz, 1H), 4.45–4.33 (m, 2H), 4.29 (q, J = 6.7 Hz, 4H), 4.13 (q, J = 6.3 Hz, 2H), 0.87 (s, 9H), 0.08 (s, 3H), 0.05 (s, 3H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 162.5, 156.6 (d, J = 7.2 Hz), 149.6, 143.0, 141.6, 141.5, 138.9, 128.2, 127.3, 125.1, 125.1, 120.2, 120.2, 104.0, 103.5, 93.3, 80.3, 69.6 (d, J = 6.2 Hz), 61.3 (d, J = 4.7 Hz), 48.00 (d, J = 8.1 Hz), 25.8, 18.2, −4.6; ³¹ P NMR (202 MHz, CDCl ₃ ) δ −1.6; HRMS (ESI+): Calculated for: C ₄₃ H ₄₅ N ₂ O ₈ NaPSi 799.2580. Found [M + Na] ⁺ : 799.2580. Example 44: 2′-O-(tert-Butyldimethylsilyl)-3′-deoxy-3′,4′-didehy drouridine-5′- phosphate (30) To a solution of difluorenylmethyl 2′-O-(tert-butyldimethylsilyl)-3′-deoxy-3′,4′- didehydrouridine (29) (200 mg, 0.257 mmol) in MeCN (1.3 mL) was added Et ₃ N (1.3 mL) and the reaction mixture was stirred at room temperature for 18 h. Celite ^® was added to the solution and the suspension was concentrated in vacuo to dryness for purification by dry load. Flash column chromatography (12 g silica gel, 10%–100% (20% conc aq NH ₄ OH in MeOH)-EtOAc) afforded the purified monophosphate as an ammonium salt, which was then concentrated from MeOH and Et ₃ N three times to afford the title compound (116 mg, 86% yield) as a colourless foam. ¹ H NMR (500 MHz, Methanol-d4) δ 7.44 (d, J = 8.1 Hz, 1H), 6.25 (d, J = 2.1 Hz, 1H), 5.73 (d, J = 8.1 Hz, 1H), 5.34 (d, J = 2.6 Hz, 1H), 4.99 (t, J = 2.4 Hz, 1H), 4.57–4.43 (m, 2H), 3.11 (q, J = 7.2 Hz, 6H), 1.29 (t, J = 7.3 Hz, 9H), 0.90 (s, 9H), 0.12 (s, 3H), 0.10 (s, 3H); ¹³ C NMR (126 MHz, Methanol-d ₄ ) δ 165.9, 161.0 (d, J = 9.5 Hz), 151.8, 141.6, 103.7, 102.9, 94.4, 81.7, 60.5 (d, J = 4.3 Hz), 47.4, 26.2, 18.9, 9.2, −4.5, −4.6; ³¹ P NMR (202 MHz, Methanol-d4) δ 1.6; HRMS (ESI+): Calculated for: C ₁₅ H25N ₂ O8NaSiP 443.1015. Found [M + Na] ⁺ : 443.1021. Example 45: 3′-Deoxy-3′,4′-didehydrouridine-5′-phosphate (31) To a solution of 2′-O-(tert-butyldimethylsilyl)-3′-deoxy-3′,4′-didehy drouridine-5′- phosphate triethylamine salt (30) (15 mg, 28.8 µmol) in deionized water (2.0 mL) was added Dowex® 50WX8 hydrogen form (30 mg), which had previously been washed with MeOH and deionized water. The suspension was stirred at room temperature for 1 h then the reaction mixture was neutralised by addition of 0.5 M aqueous triethylammonium bicarbonate (pH 7, 2 mL). The reaction mixture was filtered and the resin was washed with deionized water (3 × 1 mL). The filtrate and combined washings were lyophilized to afford the title compound (18 mg, quant) as a colourless solid. ¹ H NMR (500 MHz, D ₂ O) δ 7.58 (d, J = 8.2 Hz, 1H), 6.35 (d, J = 2.1 Hz, 1H), 5.93 (d, J = 8.1 Hz, 1H), 5.52 (d, J = 3.2 Hz, 1H), 5.03 (br s, 1H), 4.50 (d, J = 7.2 Hz, 2H), 3.26 (q, J = 7.4 Hz, 12H), 1.34 (t, J = 7.3 Hz, 18H); ¹³ C NMR (126 MHz, D ₂ O) δ 166.3, 160.1 (d, J = 8.1 Hz), 151.4, 141.5, 102.6, 100.9, 92.9, 78.5, 58.7 (d, J = 2.7 Hz), 46.7, 8.2; ³¹ P NMR (202 MHz, Methanol-d4) δ 3.7; HRMS (ESI−): Calculated for: C9H10N ₂ O8P 305.0175. Found [M − H] ⁻ : 305.0186. Example 46: 2′-O-(tert-Butyldimethylsilyl)-3′-deoxy-3′,4′-didehy drouridine-5′- triphosphate triethylammonium salt (32) 2′-O-(tert-Butyldimethylsilyl)-3′-deoxy-3′,4′-didehy drouridine-5′-phosphate triethylammonium salt (30) (150 mg, 0.288 mmol) and CDI (245 mg, 1.44 mmol) were dissolved in MeCN (3.0 mL) under argon and stirred at room temperature for 1 h, then excess CDI was quenched by addition of H ₂ O (45 µL, 2.5 mmol). The reaction mixture was stirred for 40 min, then bis(tributylammonium) pyrophosphate (790 mg, 1.44 mmol) and Bu ₃ N (0.14 mL, 0.58 mmol) were added and the reaction mixture stirred for a further 72 h, after which the reaction was complete by TLC analysis (silica gel, 6:1:3 i-PrOH-H ₂ O-28% aq NH ₄ OH). The reaction solvent was removed in vacuo, then the crude residue was purified by flash chromatography on C18 silica gel (40–80% solvent B-buffer, where buffer A is 20 mM Bu ₃ N and 30 mM AcOH in H ₂ O, solvent B is 15 mM Bu ₃ N in MeOH). The triphosphate was converted to its triethylammonium salt by passage through an ion exchange column (Dowex ^® 50WX8 Et ₃ NH form) eluting with DI H ₂ O, then lyophilized to afford the title compound (143 mg, 50% yield) as a colourless solid. ¹ H NMR (500 MHz, D ₂ O) δ 7.58 (d, J = 8.0 Hz, 1H), 6.39 (d, J = 2.2 Hz, 1H), 5.97 (d, J = 8.0 Hz, 1H), 5.63 (d, J = 2.7 Hz, 1H), 5.24 (t, J = 2.4 Hz, 1H), 4.76–4.67 (m, 2H), 3.26 (q, J = 7.3 Hz, 24H), 1.97 (d, J = 1.3 Hz, 1H), 1.34 (t, J = 7.3 Hz, 36H), 0.96 (s, 9H), 0.22 (s, 3H), 0.20 (s, 3H); ³¹ P NMR (202 MHz, D ₂ O) δ −10.09 (d, J = 18.7 Hz), −11.46 (d, J = 19.9 Hz), −23.16 (t, J = 20.2 Hz); HRMS (ESI−): Calculated for C ₁₅ H26N ₂ O14P3Si: 579.0366. Found [M − H] ⁻ : 579.0374. Example 47: 3′-Deoxy-3′,4′-didehydrouridine-5′-triphosphate tributylammonium salt (33) To a solution of 2′-O-(tert-butyldimethylsilyl)-3′-deoxy-3′,4′-didehy drouridine-5′- triphosphate triethylammonium salt (32) (76 mg, 0.077 mmol) in deionized water (8 mL) was added Dowex® 50WX8 H-form (160 mg), which had previously been washed with MeOH and deionized water. The suspension was stirred at room temperature for 1 h then the reaction mixture was neutralised by addition of Et ₃ N (0.2 mL) and stirred for a further 5 min. The reaction mixture was filtered and the resin was washed with deionized water (3 × 5 mL). The filtrate and combined washings were concentrated in vacuo at 40 ℃. The crude residue was purified by flash chromatography on C18 silica gel (15–60% solvent B- buffer, where buffer A is 20 mM Bu ₃ N and 30 mM AcOH in H ₂ O, solvent B is 15 mM Bu ₃ N in MeOH) then lyophilized to afford the title compound (52 mg, 56% yield) as a colourless solid. To facilitate characterisation, a portion of the product was converted to its sodium salt form by passage through Dowex® 50WX8 Na-form. ¹ H NMR (Bu ₃ NH ⁺ salt form) (500 MHz, D ₂ O) δ 7.48 (d, J = 8.1 Hz, 1H), 6.29 (d, J = 2.1 Hz, 1H), 5.86 (d, J = 8.1 Hz, 1H), 5.55– 5.49 (m, 1H), 4.95 (t, J = 2.4 Hz, 1H), 4.68–4.59 (m, 2H), 3.17–3.05 (m, 24H), 1.71–1.58 (m, 24H), 1.35 (h, J = 7.5 Hz, 24H), 0.91 (t, J = 7.4 Hz, 36H); ¹ H NMR (Na ⁺ salt form) (500 MHz, D ₂ O) δ 7.56 (d, J = 8.1 Hz, 1H), 6.38 (d, J = 2.0 Hz, 1H), 5.95 (d, J = 8.1 Hz, 1H), 5.61 (dt, J = 2.4, 1.1 Hz, 1H), 5.05 (t, J = 2.4 Hz, 1H), 4.78–4.71 (m, 2H); ¹³ C NMR (Na ⁺ salt form) (126 MHz, D ₂ O) δ 166.3, 158.5 (d, JCP = 7.8 Hz), 151.3, 141.4, 102.7, 102.0, 92.9, 78.5, 60.3 (d, JCP = 4.7 Hz); ³¹ P NMR (Na ⁺ salt form) (202 MHz, D ₂ O) δ −9.90 (d, J = 14.9 Hz), −11.27 (d, J = 19.3 Hz), −22.82 (t, J = 18.7 Hz); HRMS (ESI−): Calculated for C9H12N ₂ O14P3: 464.9501. Found [M − H] ⁻ : 464.9510. Example 48: 2′,5′-Bis-O-(tert-butyldimethylsilyl)-3′-deoxy-3′,4� ��-didehydrouridine (34) To a solution of iodide 23 (250 mg, 0.429 mmol) in PhMe (3 mL) was added DABCO (150 mg, 1.27 mmol), then the reaction mixture was heated to 80 °C and stirred for 18 h. The reaction mixture was cooled down to room temperature and washed with 1 M aq Na ₂ S ₂ O ₃ solution. The organic layer was then dried over anhydrous MgSO ₄ , filtered and concentrated in vacuo. Purification by flash column chromatography (silica gel, 0−30% EtOAc/Hex, then isocratic elution with 30% EtOAc/Hex) afforded the title compound (167 mg, 86%) as an off-white crystalline solid. ¹ H NMR (500 MHz, CDCl ₃ ) δ 9.26 (s, 1H), 7.18 (d, J = 5.7 Hz, 1H), 6.29–6.25 (m, 1H), 5.69 (d, J = 6.4 Hz, 1H), 5.18–5.14 (m, 1H), 4.82–4.78 (m, 1H), 4.26 (s, 2H), 0.91 (s, 9 H), 0.89 (s, 9H), 0.12 (s, 3 H), 0.10 (s, 6 H), 0.08 (s, 3H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 163.3, 161.8, 150.0, 139.2, 102.9, 101.2, 93.0, 80.5, 58.4, 25.9, 25.8, 18.4, 18.2, −4.5, −4.6, −5.25, −5.31; HRMS (ESI+): Calculated for C ₂₁ H ₃₈ N ₂ O ₅ NaSi ₂ : 477.2211. Found [M + Na] ⁺ : 477.2225. Example 49: 2′,5′-Bis-O-(tert-butyldimethylsilyl)-3′-deoxy-3′,4� ��-didehydro-4-N- hydroxycytidine (35) To a solution of uridine 34 (97 mg, 0.21 mmol) in anhydrous CH ₂ Cl ₂ (2.5 mL) at 0 °C was added DMAP (5.0 mg, 41 µmol) followed by DIPEA (200 μL, 1.14 mmol). A solution of 2,4,6-triisopropylbenzenesulfonyl chloride (165 mg, 0.534 mmol) in anhydrous CH ₂ Cl ₂ (2.5 mL) was added dropwise, then the reaction mixture was stirred at room temperature for 18 h. The reaction mixture was cooled down to 0 °C, then DIPEA (160 μL, 0.916 mmol) and hydroxylamine hydrochloride (65 mg, 0.93 mmol) were added sequentially. The reaction was allowed to warm to room temperature and stirred for a further 3 h, then quenched by addition of water and extracted with CH ₂ Cl ₂ . The organic extract was washed with brine, dried over anhydrous MgSO ₄ , filtered and concentrated in vacuo. Purification by flash column chromatography (silica gel, 0−40% EtOAc/Hex, then isocratic elution with 40% EtOAc-Hex) afforded the title compound (71 mg, 71%) as an off- white crystalline solid. ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.51 (s, 1H), 7.67 (s, 1H), 6.48 (d, J = 8.2 Hz, 1H), 6.28 (d, J = 2.1 Hz, 1H), 5.60 (d, J = 8.2 Hz, 1H), 5.14–5.09 (m, 1H), 4.87– 4.82 (m, 1H), 4.24 (s, 2H), 0.91 (s, 9H), 0.89 (s, 9H), 0.12–0.09 (3s, 9H), 0.08 (s, 3H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 162.2, 149.0, 145.3, 130.1, 100.4, 99.3, 92.8, 80.2, 58.6, 25.9, −4.5, −5.3; HRMS (ESI+): Calculated for C ₂₁ H ₄₀ N ₃ O ₅ Si ₂ : 470.2501. Found [M + H] ⁺ : 470.2511. Example 50: 3′-Deoxy-3′,4′-didehydro-4-N-hydroxycytidine (36) To a solution of compound 35 (50.0 mg, 0.11 mmol, 1.00 equiv.) in anhydrous THF (0.5 mL), triethylamine trihydrofluoride (35 μL, 0.21 mmol, 2.0 eq.) was added and the reaction mixture was stirred at room temperature under argon for 24 h. The reaction mixture was concentrated in vacuo and purified by flash column chromatography (normal phase silica gel, 0-15% MeOH/DCM) to afford compound 36 as a white solid (22 mg, 86% yield). ¹ H NMR (500 MHz, MeOD) δ 6.59 (d, J = 8.2 Hz, 1H), 6.26 (d, J = 2.4 Hz, 1H), 5.61 (d, J = 8.2 Hz, 1H), 5.21 (d, J = 2.4 Hz, 1H), 4.88 – 4.83 (m, 1H), 4.15 (s, 2H); ¹³ C NMR (126 MHz, MeOD) δ 163.9, 151.1, 146.0, 131.0, 100.6, 100.5, 93.9, 79.6, 58.0; HRMS (ESI+): Calculated for C ₉ H ₁₂ N ₃ O ₅ : 242.0771. Found [M + H] ⁺ : 242.0781. Example 51: 2′,5′-Bis-O-(tert-butyldimethylsilyl)-2-N-isobutyryl-gua nosine (38) 2-N-Isobutyryl-guanosine (37) (4.04 g, 11.2 mmol) and TBDMSCl (4.15 g, 27.3 mmol) were dissolved in DMF (65 mL), then treated with imidazole (3.02 g, 44.0 mmol) at room temperature. The reaction mixture was stirred for 3 d, then partitioned between water (100 mL) and EtOAc (150 mL). The organic layer was washed with 0.5 M aq HCl (100 mL), brine, dried over anhydrous MgSO ₄ , filtered and concentrated in vacuo. The crude oil obtained was purified by flash column chromatography on high performance silica gel (0%–15% acetone-CH ₂ Cl ₂ ) to afford the title compound (834 mg, 13% yield) as a colourless foam. ¹ H NMR (500 MHz, DMSO-d6) δ 12.08 (br s, 1H), 11.66 (br s, 1H), 8.10 (s, 1H), 5.87 (d, J = 6.6 Hz, 1H), 5.11 (d, J = 4.7 Hz, 1H), 4.45 (dd, J = 6.6, 4.8 Hz, 1H), 4.10–4.06 (m, 1H), 4.02 (q, J = 3.7 Hz, 1H), 3.86–3.75 (m, 2H), 2.76 (hept, J = 7.0 Hz, 1H), 1.11 (d, J = 6.9 Hz, 6H), 0.89 (s, 9H), 0.72 (s, 9H), 0.08 (s, 3H), 0.08 (s, 3H), −0.07 (s, 3H), −0.19 (s, 3H). Example 52: 9-(2′,5′-Bis-O-(tert-butyldimethylsilyl)-3′-iodo-β- ^D -threo- pentofuranosyl)-2-N-isobutyrylguanine (39) To a solution of PPh3 (94 mg, 0.35 mmol), I2 (90 mg, 0.35 mmol) and imidazole (47 mg, 0.68 mmol) in THF (2.5 mL) at room temperature was added a solution of 2′,5′- bis-O-(tert-butyldimethylsilyl)-2-N-isobutyryl-guanosine (29) (100 mg, 0.17 mmol) in THF (1.7 mL). The reaction mixture was heated to 60 °C and stirred for 5 h, then cooled to room temperature. The crude reaction mixture was decanted from precipitated triphenylphosphine oxide, then concentrated in vacuo. The crude product was purified by flash column chromatography (silica gel, 0%–10% acetone-CH ₂ Cl ₂ ) to afford the title compound (70 mg, 59% yield) as a colourless solid. ¹ H NMR (500 MHz, CDCl ₃ ) δ 11.95 (s, 1H), 8.19 (s, 1H), 8.14 (s, 1H), 5.70 (d, J = 2.3 Hz, 1H), 4.87 (t, J = 5.3 Hz, 1H), 4.29 – 4.24 (m, 1H), 4.05 (dd, J = 9.5, 4.3 Hz, 1H), 4.01–3.96 (m, 1H), 3.89 (dd, J = 11.0, 4.4 Hz, 1H), 2.62 (hept, J = 6.6 Hz, 1H), 1.27 (d, J = 6.7 Hz, 3H), 1.25 (d, J = 4.6 Hz, 3H), 0.95 (s, 9H), 0.84 (s, 9H), 0.18 (s, 3H), 0.16 (s, 3H), 0.10 (s, 3H), −0.14 (s, 3H); HRMS (ESI+): Calculated for C26H ₄ 7N ₅ O ₅ Si ₂ I: 692.2160. Found [M + H] ⁺ : 692.2158. Example 53: 9-(2′-O-(tert-Butyldimethylsilyl)-3′-iodo-β-D-threo-pen tofuranosyl)- 2-N-isobutyrylguanine (40) To a solution of 9-(2′,5′-bis-O-(tert-butyldimethylsilyl)-3′-iodo-β-D- threo- pentofuranosyl)-2-N-isobutyrylguanine (39) (137 mg, 198 µmol) in THF (0.6 mL) at 0 °C was added a mixture of TFA-H ₂ O (1:1, 130 µL) dropwise. The reaction mixture was allowed to warm to room temperature slowly, then stirred for 3 h. The reaction was then diluted with EtOAc (10 mL) and neutralised by addition of sat aq NaHCO ₃ (2 mL). The biphasic mixture was separated, then the organic layer was washed with water, brine, dried over anhydrous MgSO ₄ , filtered and concentrated in vacuo. The crude product obtained was purified by flash column chromatography (silica gel, 5% MeOH-EtOAc) to afford the title compound (96 mg, 84% yield) as a colourless solid. ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.23 (s, 1H), 9.27 (s, 1H), 7.91 (s, 1H), 5.50 (d, J = 6.1 Hz, 1H), 5.09 (br s, 1H), 5.00 (t, J = 6.9 Hz, 1H), 4.37 (t, J = 7.7 Hz, 1H), 4.24 (d, J = 10.4 Hz, 1H), 4.13–3.99 (m, 2H), 2.73 (p, J = 6.9 Hz, 1H), 1.24 (d, J = 7.0 Hz, 3H), 1.20 (d, J = 6.9 Hz, 3H), 0.78 (s, 9H), 0.05 (s, 3H), −0.37 (s, 3H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 179.3, 155.4, 148.2, 147.5, 139.0, 122.3, 90.0, 80.9, 80.1, 66.4, 36.4, 25.8, 25.6, 19.3, 18.9, 17.8, −3.8, −5.1; HRMS (ESI+): Calculated for C ₂₀ H ₃₃ N ₅ O ₅ SiI: 578.1296. Found [M + H] ⁺ : 578.1304. Example 54: 2′-O-(tert-Butyldimethylsilyl)-3′-deoxy-3′,4′-didehy dro-2-N- isobutyryl-guanosine (41) To a suspension of 9-(2′-O-(tert-butyldimethylsilyl)-3′-iodo-β- ^D -threo- pentofuranosyl)-2-N-isobutyrylguanine (40) (26 mg, 45.0 µmol) in PhMe (1 mL) at room temperature was added DABCO (17 mg, 150 µmol) and the resulting mixture was heated to 75 °C for 4 h. The reaction mixture was cooled to room temperature, then filtered through a pad of Celite ^® , washing with 20% EtOAc-PhMe. The filtrate was concentrated in vacuo, then the residue obtained was purified by flash column chromatography (silica gel, 5% MeOH- EtOAc) to afford the title compound (14 mg, 69% yield) as a colourless solid. ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.08 (s, 1H), 9.18 (s, 1H), 7.72 (s, 1H), 6.12 (d, J = 2.3 Hz, 1H), 5.29 (s, 1H), 5.26 (dt, J = 2.4, 1.1 Hz, 1H), 5.10 (t, J = 2.4 Hz, 1H), 4.30 (s, 2H), 3.74 (br s, 1H), 2.72 (hept, J = 6.9 Hz, 1H), 1.27 (d, J = 6.7 Hz, 3H), 1.26 (d, J = 6.4 Hz, 4H), 0.85 (s, 9H), 0.03 (s, 3H), 0.02 (s, 3H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 179.1, 161.7, 155.7, 148.0, 136.6, 121.1, 100.3, 92.2, 80.7, 57.8, 36.6, 25.9, 19.1, 18.2, −4.3, −4.4; HRMS (ESI+): Calculated for C ₂₀ H ₃₂ N ₅ O ₅ Si: 450.2173. Found [M + H] ⁺ : 450.2172. Example 55: Difluorenylmethyl-2′-O-(tert-butyldimethylsilyl)-3′-deox y-3′,4′- didehydro-2-N-isobutyryl-guanosine-5′-phosphate (42) To a solution of 2′-O-(tert-butyldimethylsilyl)-3′-deoxy-3′,4′-didehy dro-2-N- isobutyryl-guanosine (41) (613 mg, 1.36 mmol) in MeCN (6.8 mL) at room temperature was added difluorenyl N,N-diisopropylphosphoramidite (1.0 M in benzene, 1.6 mL, 1.6 mmol) and 1H-tetrazole (0.45 M in MeCN, 6.1 mL, 2.7 mmol). The reaction mixture was stirred for 1 h, then cooled to 0 ℃, and tert-butyl hydroperoxide (70 w/w% in H ₂ O, 0.38 mL, 2.7 mmol) was added dropwise. The reaction mixture was allowed to warm to room temperature and stirred for 3 h, then quenched by addition of 10% aq Na ₂ S ₂ O ₃ (2 mL) and sat aq NaHCO ₃ (50 mL). The reaction mixture was extracted with EtOAc (3 × 30 mL) and the combined organic layers were washed with brine (30 mL), dried over anhydrous MgSO ₄ , filtered and concentrated in vacuo. The crude oil was purified by flash column chromatography on silica gel (0–40% acetone-PhMe) to afford the title compound (750 mg, 62% yield) as a pale yellow foam. ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.14 (s, 1H), 10.11 (s, 1H), 7.77–7.69 (m, 4H), 7.62 (s, 1H), 7.53–7.33 (m, 8H), 7.30–7.19 (m, 4H), 5.99 (d, J = 2.3 Hz, 1H), 5.20 (dd, J = 2.6, 1.3 Hz, 1H), 4.95 (dtt, J = 2.5, 1.6, 0.7 Hz, 1H), 4.60–4.51 (m, 1H), 4.45–4.20 (m, 4H), 4.13 (dt, J = 24.7, 6.5 Hz, 2H), 2.64 (hept, J = 6.9 Hz, 1H), 1.18–1.10 (m, 6H), 0.86 (s, 9H), 0.01 (s, 3H), 0.00 (s, 3H); ¹³ C NMR (101 MHz, CDCl ₃ ) δ 179.6, 156.69 (d, JCP = 3.9 Hz), 155.7, 148.3, 147.9, 142.9–142.6 (m, 2 × C), 141.51, 141.47, 136.9, 128.3, 128.2, 127.30, 127.27, 127.2, 125.0, 124.91, 124.87, 124.8, 122.5, 120.32, 120.29, 101.5, 94.7, 81.3, 69.9–69.8 (m, 2 × C), 61.78 (d, JCP = 5.0 Hz), 47.9– 47.8 (m, 2 × C), 35.9, 25.8, 19.1, 19.0, 18.1, −4.3, −4.4; ³¹ P NMR (202 MHz, CDCl ₃ ) δ −1.6; HRMS (ESI/Q-TOF) m/z [M + H] ⁺ Calcd for C48H53N ₅ O8PSi: 886.3401; Found 886.3409. Example 56: 2′-O-(tert-Butyldimethylsilyl)-3′-deoxy-3′,4′-didehy droguanosine-5′- phosphate (43) Difluorenylmethyl-2′-O-(tert-butyldimethylsilyl)-3′-deox y-3′,4′-didehydro-2-N- isobutyryl-guanosine-5′-phosphate (42) (420 mg, 0.474 mmol) was dissolved in ammonia (7 M in MeOH, 5 mL) and stirred at room temperature for 20 h. The reaction mixture was concentrated in vacuo, then the residue obtained was purified by flash column chromatography on silica gel (20–100% solvent B-EtOAc, where B is 5% conc aq NH ₄ OH in MeOH). The product thus obtained was coevaporated from MeOH and Et ₃ N three times, then lyophilized from water to afford the title compound (201 mg, 76% yield) as a colourless solid. ¹ H NMR (400 MHz, Methanol-d4) δ 7.80 (s, 1H), 6.20 (d, J = 2.5 Hz, 1H), 5.38 (dt, J = 2.4, 1.1 Hz, 1H), 5.32 (tt, J = 2.4, 1.1 Hz, 1H), 4.48 (dt, J = 6.1, 1.2 Hz, 2H), 3.06 (q, J = 7.3 Hz, 6H), 1.25 (t, J = 7.3 Hz, 9H), 0.88 (s, 9H), 0.07 (s, 3H), 0.07 (s, 3H); ¹³ C NMR (101 MHz, Methanol-d4) δ 160.8 (d, J = 10.3 Hz), 159.4, 155.7, 152.9, 136.8, 117.4, 102.0, 92.8, 81.5, 60.5 (d, J = 3.7 Hz), 47.2, 26.2, 18.9, 9.3, −4.4, −4.5; ³¹ P NMR (162 MHz, Methanol-d4) δ 1.7; HRMS (ESI/Q-TOF) m/z [M + H] ⁺ Calcd for C ₁₆ H ₂₇ N ₅ O ₇ PSi: 460.1417; Found 460.1425. Example 57: 3′-Deoxy-3′,4′-didehydroguanosine-5′-triphosphate triethylammonium salt (44) 2′-O-(tert-Butyldimethylsilyl)-3′-deoxy-3′,4′-didehy droguanidine-5′-phosphate triethylammonium salt (43) (172 mg, 0.307 mmol) and CDI (265 mg, 1.55 mmol) were dissolved in MeCN (3.0 mL) and DMF (1.5 mL) under argon. The reaction mixture was stirred at room temperature for 2 h, then excess CDI was quenched by addition of H ₂ O (50 µL, 3 mmol). The reaction mixture was stirred for 1 h, then passed through a Dowex ^® 50WX8 Et ₃ NH-form column to remove imidazole, eluting with MeCN. The eluted phosphorimidazolidate intermediate was concentrated in vacuo, brought under argon, redissolved in DMF (3.0 mL) and treated with bis(tributylammonium) pyrophosphate (500 mg, 0.911 mmol). The reaction mixture was stirred at room temperature for 48 h, then concentrated in vacuo. The residue was purified by flash column chromatography on C18 silica gel (20–80% solvent B-buffer, where buffer A is 20 mM Bu ₃ N and 30 mM AcOH in H ₂ O, solvent B is 15 mM Bu ₃ N in MeOH) and lyophilized. The triphosphate was converted to its triethylammonium salt salt by passage through an ion exchange column (Dowex ^® 50WX8 Et ₃ NH form), then lyophilized to afford the title compound (123 mg, 44% yield) as a colourless solid. ¹ H NMR (400 MHz, D ₂ O) δ 7.86 (s, 1H), 6.32 (d, J = 2.0 Hz, 1H), 5.62 (dd, J = 2.5, 1.2 Hz, 1H), 5.19 (ddt, J = 2.9, 2.0, 1.0 Hz, 1H), 4.73–4.62 (m, 2H), 3.20 (q, J = 7.3 Hz, 24H), 1.28 (t, J = 7.3 Hz, 36H); ¹³ C NMR (101 MHz, D ₂ O) δ 158.8, 158.2 (d, JCP = 8.6 Hz), 154.0, 151.1, 136.7, 115.8, 101.3, 90.9, 78.2, 60.3 (d, JCP = 4.9 Hz), 46.6, 8.2; ³¹ P NMR (Na ⁺ salt form) (162 MHz, D ₂ O) δ −5.93 (d, J = 20.4 Hz), −11.07 (d, J = 19.0 Hz), −21.95 (t, J = 19.4 Hz); HRMS (ESI/Q-TOF) m/z [M − H] ⁻ Calcd for C ₁₀ H ₁₃ N ₅ O ₁₃ P ₃ : 503.9723; Found 503.9730. Example 58: 2′,5′-Bis-O-(tert-butyldimethylsilyl)-5-azacytidine (46) To a suspension of 5-azacytidine (45) (2.50 g, 10.2 mmol) in pyridine (20.5 mL) at room temperature was added TBDMSCl (4.81 g, 31.0 mmol) in one portion. The reaction mixture was stirred for 48 h, then concentrated in vacuo. The oil obtained was triturated with EtOAc (100 mL), then filtered through Celite ^® and the filtrate was washed sequentially with sat. aq. NaHCO ₃ (25 mL), water (25 mL) and brine (25 mL). The organic phase was dried over anhydrous MgSO ₄ , filtered and concentrated in vacuo with approximately 10 g of silica gel, to afford a free-flowing mixture for dry loading. Purification by flash column chromatography on silica gel (5:45:50 MeOH-EtOAc-Hex) afforded the title compound (1.74 g, 36% yield) as a colourless solid. ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.69 (s, 1H), 6.65 (s, 1H), 5.85 (d, J = 2.2 Hz, 1H), 5.62 (s, 1H), 4.25 (dd, J = 4.7, 2.1 Hz, 1H), 4.17 (ddd, J = 8.7, 6.9, 4.7 Hz, 1H), 4.08 (dd, J = 11.7, 2.0 Hz, 1H), 4.03 (dt, J = 6.9, 1.9 Hz, 1H), 3.86 (dd, J = 11.7, 1.8 Hz, 1H), 2.45 (d, J = 8.7 Hz, 1H), 0.94 (s, 9H), 0.92 (s, 9H), 0.25 (s, 3H), 0.15 (s, 3H), 0.14 (s, 3H), 0.13 (s, 3H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 166.4, 156.3, 153.8, 90.0, 84.6, 76.9, 68.9, 61.6, 26.1, 25.9, 18.7, 18.2, −4.3, −5.28, −5.31, −5.4; HRMS (ESI/Q-TOF) m/z [M + H] ⁺ Calcd for C20H ₄ 1N ₄ O ₅ Si ₂ : 473.2615. Found 464.2021. Example 59: 2′,5′-Bis-O-(tert-butyldimethylsilyl)-4-N-(4,4′-dimeth oxytrityl)-5- azacytidine (47) 2′,5′-Bis-O-(tert-butyldimethylsilyl)-5-azacytidine (46) (1.55 g, 3.28 mmol), 4,4′- dimethoxytrityl chloride (1.29 g, 3.62 mmol) and AgNO3 (613 mg, 3.60 mmol) were placed under argon, then dissolved in CH ₂ Cl ₂ (33 mL). The resulting solution was treated with sym- collidine (0.90 mL, 6.81 mmol), upon which a precipitate formed and the reaction mixture turned orange. The reaction mixture was stirred at room temperature for 90 min, after which the colour of the mixture had changed to yellow-brown. The reaction mixture was filtered through a pad of Celite ^® , washing with CH ₂ Cl ₂ (2 × 10 mL), then the filtrate was concentrated in vacuo. The residue obtained was dissolved in EtOAc (125 mL) and washed sequentially with 10% aq. CuSO ₄ (3 × 30 mL), 5% aq. EDTA (2 × 25 mL) and brine (25 mL), then the organic phase was dried over anhydrous MgSO ₄ , filtered and concentrated in vacuo with silica gel (approx 10 g) for purification by dry load. Flash column chromatography on silica gel (20–50% EtOAc-Hex) afforded the title compound (2.44 g, 96% yield) as a colourless solid. The product existed as a 3:2 mixture of rotamers, designated as A (major) and B (minor), respectively. ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.54 (s, 0.4H, B), 8.41 (s, 0.6H, A), 7.29–7.11 (m, 9H A + B), 6.80–6.75 (m, 4.6 H), 6.63 (brs, 0.4H, B), 5.84 (d, J = 2.3 Hz, 1H, A), 5.75 (d, J = 2.5 Hz, 1H, B), 4.19–3.76 (m, 12H, A + B); 2.44 (d, J = 7.4 Hz, 0.4H, B), 2.41 (d, J = 8.1 Hz, 0.6H, A), 0.94 (s, 3.6H, B), 0.92 (s, 5.4H, A), 0.88 (s, 3.6H, B), 0.76 (s, 5.4H, A), 0.23 (s, 1.8H, A), 0.14–0.12 (m, 5.4H, A + B), 0.06 (s, 1.2H, B), −0.04 (s, 1.8H, A), −0.09 (s, 1.8H, A); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 165.6 (A), 163.7 (B), 158.42 (B), 158.37 (A), 155.0 (A), 154.7 (B), 153.7 (A), 152.7 (B), 145.2 (A), 144.7 (B), 137.4 (B), 137.3 (A), 136.7 (A + B), 130.3 (A + B), 130.04 (B), 129.99 (A), 128.8 (B), 128.6 (A), 128.0 (B), 127.9 (A), 126.91 (B), 126.86 (A), 113.2 (A + B), 89.6 (A), 89.5 (B), 84.6 (B), 84.5 (A), 77.0 (A), 76.9 (B), 70.5 (A + B), 69.4 (B), 69.1 (A), 61.9 (B), 61.6 (A), 55.3 (A + B), 26.2 (B), 26.0 (A), 25.93 (A), 25.88 (B), 18.6 (B), 18.5 (A), 18.2 (A), 18.1 (B), −4.4 (A), −4.5 (B), −5.3 (A + B), −5.4 (B), −5.5 (A + B); HRMS (ESI/Q-TOF) m/z [M + Na] ⁺ Calcd for C ₄₁ H ₅₈ N ₄ NaO ₇ Si ₂ : 797.3742. Found 797.3738. Example 60: 2′,5′-Bis-O-(tert-butyldimethylsilyl)-3′-iodo-β-D-xyl ofuranosyl)-4-N- (4,4′-dimethoxytrityl)-5-azacytosine (48) To a solution of PPh3 (1.49 g, 5.62 mmol), imidazole (775 mg, 11.2 mmol) and iodine (1.43 g, 5.63 mmol) in THF (40 mL) at room temperature was added a solution of 2′,5′-bis-O-(tert-butyldimethylsilyl)-4-N-(4,4′-dimeth oxytrityl)-5-azacytidine (47) (2.19 g, 2.82 mmol) in THF (28 mL). The reaction mixture was heated to 60 °C and stirred for 18 h. The reaction mixture was then cooled to room temperature, diluted with EtOAc-Hex (2:1, 75 mL), and filtered through a pad of Celite ^® . The filtrate was concentrated in vacuo, then the resulting residue was purified by flash column chromatography on silica gel (25−40% EtOAc-Hex) to afford the title compound (2.32 g, 93% yield) as a colourless foam. The product existed as an approximately 2:1 mixture of rotamers, designated as A (major) and B (minor), respectively. ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.35 (s, 0.33H, B), 8.14 (s, 0.66H, A), 7.29–7.12 (m, 9H, A + B), 6.81–6.75 (m, 4H, A + B), 6.74 (s, 0.66H, A), 6.65 (s, 0.33H, B), 5.65 (d, J = 1.5 Hz, 0.66H, A), 5.60 (d, J = 2.1 Hz, 0.33H, B), 4.67 (t, J = 1.9 Hz, 0.66H, A), 4.64 (t, J = 2.4 Hz, 0.33H, B), 4.12 (dd, J = 4.5, 2.7 Hz, 0.33H, B), 4.05 (dd, J = 4.2, 2.1 Hz, 0.66H, A), 4.03–3.88 (m, 2H, A + B), 3.82–3.74 (m, 6.33H, A + B), 3.64 (td, J = 7.5, 3.1 Hz, 0.66H, A), 0.93 (s, 3H, B), 0.89 (s, 6H, A), 0.86 (s, 9H, A + B), 0.16 (s, 2H, A), 0.14 (s. 1H, B). 0.13 (s, 3H, A + B), 0.09 (s, 1H, B), 0.06 (s, 2H, A + B), 0.05 (s, 2H, A); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 166.0 (A), 163.8 (B), 158.4 (A), 154.9 (B), 154.4 (A + B), 153.7 (A), 152.8 (B), 145.2 (A), 144.7 (B), 137.30 (A), 137.27 (A), 136.6 (B), 130.2 (B), 130.0 (A), 128.8 (B), 128.7 (A), 128.0 (A + B), 126.99 (A), 126.96 (B), 113.3 (A + B), 92.5 (A), 92.0 (B), 83.1 (A), 82.9 (B), 82.0 (A), 81.4 (B), 70.74 (A), 70.68 (B), 67.8 (B), 67.5 (A), 55.3 (A + B), 29.9 (A), 29.6 (B), 26.1 (B), 26.0 (A), 25.8 (A), 25.7 (B), 18.5 (B), 18.4 (A), 17.91 (A), 17.86 (B), −4.60 (A), −4.63 (B), −4.75 (B), −4.84 (A), −5.07 (B), −5.12 (A), −5.17 (B), −5.25 (A). HRMS (ESI/Q-TOF) m/z [M + Na] ⁺ Calcd for C ₄₁ H ₅₇ N ₄ NaO ₆ Si ₂ : 907.2759. Found 907.2754. Example 61: 2′-O-(tert-Butyldimethylsilyl)-3′-iodo-β-D-xylofuranosy l)-5- azacytosine (49) To a solution of 1-(2′,5′-bis-O-(tert-butyldimethylsilyl)-3′-iodo-β-D- xylofuranosyl)-4- N-(4,4′-dimethoxytrityl)-5-azacytosine (48) (1.50 g, 1.69 mmol) in THF (3.4 mL) at 0 °C was added a mixture of TFA-H ₂ O (1:1, 1.0 mL) dropwise. The reaction mixture was allowed to warm to room temperature and stirred for 7 h, then quenched by addition of sat aq NaHCO ₃ (40 mL). The aqueous layer was extracted with EtOAc (3 × 30 mL), then the combined organic phases were washed with brine, dried over anhydrous MgSO ₄ , filtered and concentrated in vacuo. Purification by flash column chromatography on silica gel (2–10% MeOH-EtOAc) afforded the title compound (440 mg, 55% yield) as a colourless solid. ¹ H NMR (400 MHz, DMSO-d6) δ 8.47 (s, 1H), 7.61 (s, 1H), 7.58 (s, 1H), 5.54 (d, J = 2.7 Hz, 1H), 5.14 (t, J = 5.2 Hz, 1H), 4.74 (t, J = 3.1 Hz, 1H), 4.34 (dd, J = 5.3, 3.4 Hz, 1H), 3.96 (q, J = 5.0 Hz, 1H), 3.77–3.59 (m, 2H), 0.87 (s, 9H), 0.12 (s, 3H), 0.07 (s, 3H); ¹³ C NMR (101 MHz, DMSO-d ₆ ) δ 165.9, 155.7, 153.2, 91.0, 82.3, 81.0, 66.1, 28.9, 25.5, 17.5, −4.8, −5.0; HRMS (ESI/Q-TOF) m/z [M + Na] ⁺ Calcd for C14H25N ₄ NaO ₄ Si: 491.0587. Found 491.0596. Example 62: 2′-O-tert-Butyldimethylsilyl-3′-deoxy-3′,4′-didehydr o-5- azacytosine (50) 1-(2′-O-(tert-Butyldimethylsilyl)-3′-iodo-β-D-xylofuran osyl)-5-azacytosine (498mg, 1.06^mmol) and DABCO (420 mg, 3.71mg) were suspended in PhMe (21^mL) and heated at 75^°C for 18^h. The reaction mixture was cooled to room temperature and concentrated in vacuo, then the solid residue was adsorbed onto silica gel by concentration from a solution in CH ₂ Cl ₂ -MeOH. The silica dry load thus obtained was subjected to flash column chromatography on silica gel (7−20% solvent B-EtOAc, solvent B: 20% conc NH ₄ OH in MeOH) to afford the title compound (224mg, 62% yield) as a colourless solid. ¹ H NMR (500 MHz, DMSO-d6) δ 8.02 (s, 1H), 7.62 (s, 2H), 6.04 (d, J = 2.0 Hz, 1H), 5.30 (t, J = 5.9 Hz, 1H), 5.16 (dd, J = 2.3, 1.1 Hz, 1H), 5.04 (tt, J = 2.1, 0.9 Hz, 1H), 4.06 (d, J = 5.6 Hz, 2H), 0.85 (s, 9H), 0.07 (s, 3H), 0.05 (s, 3H); ¹³ C NMR (101 MHz , DMSO-d6) δ 165.8, 161.9, 155.1, 152.5, 100.3, 93.0, 79.5, 56.0, 25.7, 17.8, −4.69, −4.67; HRMS (ESI/Q-TOF) m/z [M + Na] ⁺ Calcd for C ₁₄ H ₂₄ N ₄ O ₄ NaSi: 363.1465; Found 363.1475. Example 63: 3′-Deoxy-3′,4′-didehydro-5-azacytosine (51) To a solution of 2′-O-(tert-butyldimethylsilyl-3′-deoxy-3′,4′-didehyd ro-5-azacytosine (50) (51 mg, 0.15 mmol) in MeOH (1.5 mL) was added NH ₄ F (29 mg, 0.76 mmol) and the reaction mixture was heated to 60 °C for 1 h. The reaction was then charged with additional NH ₄ F (10 g, 0.27 mmol) and stirred at 60 °C for 1 h further. The reaction mixture was then cooled to room temperature, then the precipitate was collected by vacuum filtration, washing first with MeOH (2 × 1.5 mL), then Et2O (2 × 1.5 mL). The solid was collected and dried under high vacuum to afford the title compound (24 mg, 71% yield) as a colourless solid. ¹ H NMR (500 MHz, DMSO-d6) δ 8.00 (s, 1H), 7.60 (s, 2H), 6.03 (d, J = 2.2 Hz, 1H), 5.58 (s, 1H), 5.26 (s, 1H), 5.14 (d, J = 2.5 Hz, 1H), 4.82 (d, J = 2.8 Hz, 1H), 4.04 (s, 2H); ¹³ C NMR (126 MHz, DMSO-d6) δ 165.7, 161.2, 155.1, 152.5, 100.5, 92.9, 77.6, 56.0; HRMS (ESI/Q-TOF) m/z [M + Na] ⁺ Calcd for C ₈ H ₁₀ N ₄ NaO ₄ : 249.0600; Found 249.0594. Example 64: 4-N-Benzoyl-2′,5′-bis-O-(tert-butyldimethylsilyl)-5-fluo rocytidine (53) To a suspension of 4-N-benzoyl-5-fluorocytidine (52) (3.31 g, 9.06 mmol) in pyridine (20 mL) at room temperature was added TBDMSCl (4.22 g, 27.2 mmol). The reaction was stirred for 72 h after which the volatiles were removed in vacuo. The crude white solid was dissolved in EtOAc and washed with water (2 × 300 mL), then brine (250 mL) and was dried (MgSO ₄ ), then concentrated in vacuo. Purification by flash column chromatography on silica gel (0–18% EtOAc-pet ether over 10 column volumes) afforded the title compound as a white solid (3.45 g, 64% yield). ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.30 (dd, J = 16.9, 6.9 Hz, 3H), 7.57–7.51 (m, 1H), 7.44 (t, J = 7.7 Hz, 2H), 5.97 (dd, J = 3.9, 1.6 Hz, 1H), 4.22 (t, J = 4.1 Hz, 1H), 4.13 (q, J = 4.6 Hz, 2H), 4.05 (dd, J = 11.7, 1.6 Hz, 1H), 3.85 (dd, J = 11.7, 1.3 Hz, 1H), 2.60 (d, J = 4.8 Hz, 1H), 0.96 (s, 9H), 0.92 (s, 9H), 0.18 (s, 3H), 0.16 (s, 6H), 0.11 (s, 3H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 152.8 (d, JCF = 18.6 Hz), 146.9, 140.9, 139.0, 136.2, 133.1, 130.1, 128.4, 125.5 (d, JCF = 33.4 Hz), 89.3, 85.2, 76.8, 70.4, 62.6, 26.1, 25.8, 18.6, 18.1, −4.6, −5.2, −5.4, −5.5. ¹⁹ F NMR (471 MHz, CDCl ₃ ) δ −159.85. HRMS (ESI/QTOF) m/z: [M + Na] ⁺ : Calculated for C ₂₈ H ₄ 4FN ₃ NaO ₆ Si ₂ , 616.2645; Found 616.2651. Example 65: 1-(2′,5′-Bis-O-(tert-butyldimethylsilyl)-3′-iodo-β--t hreo- pentofuranosyl)-4-N-benzoyl-5-fluorocytosine (54) To a solid mixture of 4-N-benzoyl-2′,5′-bis-O-(tert-butyldimethylsilyl)-5- fluorocytidine (53) (1.60 g, 2.70 mmol) and triphenoxymethylphosphonium iodide (2.3 g, 4.1 mmol) was added DMF (11 mL) followed by pyridine (0.44 mL, 5.4 mmol). The reaction mixture was protected from light sources and stirred at room temperature for 48 h, after which the reaction was quenched with Et ₃ N-MeOH (1:1, 4 mL). After stirring for 10 min, H ₂ O (80 mL) was added. The aqueous mixture was extracted with EtOAc (3 × 80 mL) and the combined organic phases were washed with brine (40 mL), dried (MgSO ₄ ) and concentrated in vacuo. Partial purification by flash column chromatography on silica gel (0–10% EtOAc- pet ether over 10 column volumes) afforded an orange oil which was telescoped into the following deprotection step. ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.36–8.24 (m, 2H), 8.11 (d, J = 6.0 Hz, 1H), 7.59–7.52 (m, 1H), 7.46 (t, J = 7.6 Hz, 2H), 5.77 (dd, J = 3.4, 1.6 Hz, 1H), 4.64 (t, J = 4.1 Hz, 1H), 4.24 (t, J = 5.0 Hz, 1H), 4.10–4.02 (m, 2H), 3.95–3.87 (m, 1H), 0.97 (s, 9H), 0.90 (s, 9H), 0.20 (s, 3H), 0.18 (s, 3H), 0.16 (s, 3H), 0.09 (s, 3H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 152.8 (d, J _CF = 18.9 Hz), 146.6, 140.7, 138.5, 136.4, 133.2, 130.2, 128.5, 125.6 (d, JCF = 36.5 Hz), 90.9, 82.5, 81.0, 67.4, 28.3, 26.2, 25.7, 21.2, 18.5, 17.9, –4.3, –4.6, –5.0, –5.2; ¹⁹ F NMR (471 MHz, CDCl ₃ ) δ −160.66. HRMS (ESI/QTOF) m/z: [M + Na] ⁺ : Calculated for C ₂₈ H ₄₃ FIN ₃ NaO ₅ Si ₂ , 726.1662: Found 726.1670. Example 66: 1-(2′-O-(tert-Butyldimethylsilyl)-3′-iodo-β-D-threo-pen tofuranosyl)- 5-fluorouracil (55) To a solution of 1-(2′,5′-bis-O-(tert-butyldimethylsilyl)-3′-iodo-β-D- threo- pentofuranosyl)-4-N-benzoyl-5-fluorocytosine (54) (930 mg, 1.32 mmol) in THF (2.8 mL) at 0 °C was added TFA-H ₂ O (1:1, 0.8 mL) dropwise. After 10 min, the reaction was warmed to room temperature and stirred for 4.5 hr. The reaction was quenched by slow addition of sat aq NaHCO ₃ and the mixture was stirred for a further 10 min before being extracted with EtOAc (3 × 10 mL). The combined organic layers were washed with water (15 mL) and brine (15 mL), then dried (MgSO ₄ ), filtered, and concentrated in vacuo. Purification by flash column chromatography on silica gel (0–35% EtOAc-pet ether over 10 column volumes) afforded the title compound as a white solid (260 mg, 20% over two steps). ¹ H NMR (500 MHz, CDCl ₃ ) δ 8.77 (s, 1H), 7.99 (dd, J = 6.5, 0.8 Hz, 1H), 5.72 (dd, J = 3.2, 1.5 Hz, 1H), 4.67 (t, J = 3.6 Hz, 1H), 4.22 (ddd, J = 4.5, 4.1, 0.8 Hz, 1H), 4.17–4.04 (m, 2H), 3.95–3.87 (m, 1H), 2.09–2.03 (m, 1H), 0.89 (s, 9H), 0.15 (s, 3H), 0.09 (s, 3H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 156.8 (d, JCF = 27.1 Hz), 148.8, 141.3, 139.4, 125.0 (d, JCF = 35.0 Hz), 91.5, 83.3, 80.8, 67.3, 28.1, 25.7, 17.9, −4.3, −4.7; ¹⁹ F NMR (471 MHz, CDCl ₃ ) δ −164.45; HRMS (ESI/QTOF) m/z: [M − H] ⁻ : Calculated for C ₁₅ H23FIN ₂ O ₅ Si, 485.0410; Found 485.0449. Example 67: 2′-O-(tert-Butyldimethylsilyl)-3′-deoxy-3′,4′-didehy dro-5- fluorouridine (56) 1-(2′-O-(tert-Butyldimethylsilyl)-3′-iodo-β-D-threo-pen tofuranosyl)-5-fluorouracil (55) (246 mg, 0.506 mmol) was dissolved in dry PhMe (8.5 mL) then heated to 75 °C and treated with DABCO (170 mg, 0.506 mmol). The reaction mixture was stirred at 75 °C for 4 h, then cooled to room temperature and concentrated in vacuo. Purification by flash column chromatography on silica gel (0–35% EtOAc-pet ether over ten column volumes) afforded the title compound as a white solid (131 mg, 72%). ¹ H NMR (500 MHz, CDCl ₃ ) δ 9.73 (d, J = 4.3 Hz, 1H), 7.23 (d, J = 5.7 Hz, 1H), 6.25 (t, J = 1.5 Hz, 1H), 5.22 (dd, J = 2.4, 1.1 Hz, 1H), 4.87 (t, J = 2.1 Hz, 1H), 4.33–4.27 (m, 2H), 2.88 (d, J = 6.2 Hz, 1H), 0.88 (s, 9H), 0.10 (s, 3H), 0.08 (s, 3H); ¹³ C NMR (126 MHz, CDCl ₃ ) δ 161.4, 157.1 (d, JCF = 26.6 Hz), 148.7, 142.0, 140.1, 123.8 (d, JCF = 33.9 Hz), 101.4, 93.4, 80.4, 57.7, 25.8, 18.2, −4.5; ¹⁹ F NMR (471 MHz, CDCl ₃ ) δ −163.34; HRMS (ESI/QTOF) m/z: [M − H] ⁻ : Calculated for C ₁₅ H ₂₂ FN ₂ O ₅ Si, 357.1288 Found 357.1288. *** Although the invention has been described by way of example, it should be appreciated that variations and modifications may be made without departing from the scope of the invention as defined in the claims. Furthermore, where known equivalents exist to specific features, such equivalents are incorporated as if specifically referred in this specification.